Hematology - ION Solutions

volume 12, issue 1 - spring 2013 

oncologistics | v o l u m e 1 2 , i s s u e 1 - s p r i n g 2 0 1 3 

Hematology 

Perceptions of Triptorelin Pamoate 

and Leuprolide Acetate 

Lymphoma Highlights from ASH 2012 

Community Counts

oncologistics volume 12, issue 1 - spring 2013 

table of contents spring 2013 

02 

14 

34 

42 

Industry Insight: 

Millennium’s Mission in Oncology 

By: Melissa Bradbury 

Drug Update: 

Levo-leucovorin in Colon Cancer 

By: Sam E. Mikhail, M.D. and 

John Marshall, M.D. 

Reimbursement Watch: 

New Payment Models in Healthcare Delivery 

By: Sara Fernandez, PhD 

The Physician-Payer Relationship: Using 

Data to Drive the Future Of Oncology Care 

By: Barry Fortner, PhD 

editorial & design staff: 

> Chris Vorce 

Director, Marketing & Communications, ION Solutions 

> Melissa Bradbury 

Manager, Marketing & Communications, ION Solutions 

> Amy Migliore 

Graphic Designer, Marketing & Communications, 

ION Solutions 

article and advertising submissions: 

Article submissions and suggestions, as well as 

advertising inquiries, may be sent to: 

Chris Vorce 

Managing Editor, Oncologistics 

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3101 Gaylord Parkway 

Frisco, TX 75034 

or by e-mail: chris.vorce@iononline.com 

Information presented in Oncologistics is not intended as a substitute 

for the personalized advice given by a healthcare provider. The 

opinions expressed on the pages of Oncologistics magazine are 

those of the authors and do not necessarily reflect the views of 

ION Solutions or AmerisourceBergen Specialty Group. Although 

Oncologistics strives to present only current and accurate information, 

readers should not consider it as professional advice or endorsement 

of any position. Although great care has been taken in compiling and 

checking the information given in this publication to ensure accuracy, 

the authors, ION Solutions, and its employees or agents shall not 

be responsible or in any way liable for the continued currency of 

the information or for any errors, omissions, or inaccuracies in this 

magazine, whether arising from negligence or otherwise or for any 

consequence arising therefrom. The staff of Oncologistics provides 

columns and other editorial support. In no way are they responsible 

for the specific views presented in Oncologistics. Oncologistics 

magazine is published by ION Solutions, an AmerisourceBergen 

Specialty Group company. 

All archived issues of Oncologistics are available online 

at www.iononline.com.

oncologistics volume 12, issue 1 - spring 2013 

table of contents spring 2013 

04 

18 

30 

36 

Drug Update: 

Patient and Clinician Perceptions of 

Triptorelin Pamoate and Leuprolide Acetate 

in Patients With Advanced Prostate Cancer 

By: Neal D. Shore, MD, FACS, Paul Sieber, 

MD, FACS, Leanne Schimke, MSN, CRNP, 

FNP-C, CUNP, Adam Perzin, MD, Scott 

Olsen, MPH 


Why Community Counts 

By: Chris Vorce 


Lymphoma Review: Selected Highlights 

from ASH 2012 

By: Michael E. Williams, MD, ScM 

Reimbursement Watch: 

Getting Ready For Health Insurance 

Exchanges 

By: Zachary Bridges 

editorial & design staff: 

> Chris Vorce 

Director, Marketing & Communications, ION Solutions 

> Melissa Bradbury 

Manager, Marketing & Communications, ION Solutions 

> Amy Migliore 

Graphic Designer, Marketing & Communications, 

ION Solutions 

article and advertising submissions: 

Article submissions and suggestions, as well as 

advertising inquiries, may be sent to: 

Chris Vorce 

Managing Editor, Oncologistics 

c/o ION Solutions 

3101 Gaylord Parkway 

Frisco, TX 75034 

or by e-mail: chris.vorce@iononline.com 

oncologistics volume 12, issue 1 - spring 2013 2 

Information presented in Oncologistics is not intended as a substitute 

for the personalized advice given by a healthcare provider. The 

opinions expressed on the pages of Oncologistics magazine are 

those of the authors and do not necessarily reflect the views of 

ION Solutions or AmerisourceBergen Specialty Group. Although 

Oncologistics strives to present only current and accurate information, 

readers should not consider it as professional advice or endorsement 

of any position. Although great care has been taken in compiling and 

checking the information given in this publication to ensure accuracy, 

the authors, ION Solutions, and its employees or agents shall not 

be responsible or in any way liable for the continued currency of 

the information or for any errors, omissions, or inaccuracies in this 

magazine, whether arising from negligence or otherwise or for any 

consequence arising therefrom. The staff of Oncologistics provides 

columns and other editorial support. In no way are they responsible 

for the specific views presented in Oncologistics. Oncologistics 

magazine is published by ION Solutions, an AmerisourceBergen 

Specialty Group company. 

All archived issues of Oncologistics are available online 

at www.iononline.com. 

oncologistics 3

drug update 

PATIENT and CLINICIAN 

PERCEPTIONS of TRIPTORELIN 

PAMOATE and LEUPROLIDE 

ACETATE in PATIENTS WITH 

Advanced PROSTATE CANCER 

oncologistics drug update 

THE incidence of 

PROSTATE cancer 

HAS been decreasing 

SINCE 2004 in men aged 

≥65 yEARS, but has 

REMAINED stable in 

MEN aged

drug update 


THE study protocol was approved by an institutional 

REVIEW board and conducted in accordance with 

GOOD CLINICAL PRACTICE and all applicable codes 

AND regulations. 


regarding specific tolerability issues with different 

GnRH agonists. This study compares patients’ as well 

as clinicians’ perceptions of injection site tolerability 

following the IM injection of triptorelin pamoate or SC 

injection of leuprolide acetate. 

Methods 

Patients 

Male patients aged ≥18 years with a diagnosis of 

advanced prostate cancer for whom treatment with 

triptorelin IM or leuprolide SC is indicated were included. 

Patients had to have a life expectancy of ≥1 year and 

had to be capable of completing study questionnaires 

without assistance. Patients with a history of alcohol 

or drug abuse within the past year, patients who 

required concomitant medications that could affect 

study assessments (eg, topical medications used for 

pretreatment of injection site pain), and patients with 

known hypersensitivity to GnRH or luteinizing hormonerelease 

hormone (LHRH) agonists were excluded from 

the study. 

Study Design and Treatments 

This multicenter, randomized, crossover, open-label 

study (NCT01161563) consisted of two study periods. 

During the first study period, patients were randomized 

1:1 to receive a single injection of triptorelin pamoate 

22.5 mg mixed with 2 mL sterile water administered 

intramuscularly in either buttock or leuprolide acetate 

45 mg mixed liquid in a prefilled delivery system 

administered subcutaneously in the upper- or midabdominal 

area. Block randomization was used to 

ensure equal distribution among study centers. During 

study period 2, 24 to 26 weeks after the Period 1 clinic 

visits, patients crossed over and received the alternate 

treatment. Pretreatment of the injection site with topical 

anesthetic or analgesic agents was not permitted. 

The study protocol was approved by an institutional 

review board and conducted in accordance with 

Good Clinical Practice and all applicable codes and 

regulations. Written informed consent was obtained 

from each patient before any study procedure was 

initiated. 

Patient Perceptions 

Questionnaires assessing patient perceptions were 

administered 10 to 15 minutes after each injection. The 

primary assessment was patient bother from injection 

site burning and/or stinging, which was assessed on a 

Visual Analog Scale (VAS) from 0 (not bothered at all) 

to 10 (extremely bothered). Secondary assessments 

included patient bother from each of the following 

potential injection site effects: soreness, redness, 

bruising, itching, hardening, and swelling. These 

assessments also were done on VAS from 0 to 10. 

Other patient perceptions were assessed, including: 

discomfort experienced (0 [no discomfort] to 10 [worst 

discomfort]); anxiety prior to receiving the injection (0 

[not at all anxious] to 10 [extremely anxious]); anxiety 

about receiving another injection with the same 

product (0 [not at all anxious] to 10 [extremely anxious]); 

and overall satisfaction with injection experience (0 

[completely satisfied] to 10 [not satisfied at all]). 

Clinician Perceptions 

The clinician who prepared and administered the 

medications completed the questionnaire assessing 

clinician perceptions after each injection. Clinician 

satisfaction with the following aspects of the 

medications were assessed on a VAS from 0 (strongly 

oncologistics 7

drug update 


Table 1: Demographic and Physical Characteristics at Baseline (Per-Protocol Population) 


agree) to 10 (strongly disagree): convenience of product 

to store prior to administration; simplicity and ease of 

understanding the instructions; ease in identifying the 

components of the injection device; time required to 

set up for the injection was reasonable for the method 

of administration; ease in preparing the device prior to 

injection; ease in mixing the product using the device; 

ease in drawing the product into the syringe and 

attaching the needle; time required to prepare product 

was reasonable for the method of administration; ease in 

injecting the product; feeling protected from accidental 

needle sticks following the product administration; and the 

time required to administer the product was reasonable 

for the method of administration. 

Other caregiver assessments included: distress the 

patient experienced associated with this injection (0 [no 

distress at all] to 10 [extremely distressed]) and overall 

satisfaction with injection experience (0 [completely 

satisfied] to 10 [not satisfied at all]). 

Adverse Events 

Adverse events (AEs) were assessed for each study 

period for 24 hours after administration of study 

medication. An AE was defined as any undesirable 

medical event occurring to a patient, regardless of 

whether the event was related or unrelated to the study 

medication. Exacerbation of a pre-existing medical 

condition also was considered an AE. 

Statistical Analysis 

The study population included all patients who received 

injections of both study medications and answered 

the primary assessment question on the patient 

questionnaires following both study injections. The 

clinician population included all study site clinicians 

who administered at least 1 injection and completed at 

least 1 clinician impression questionnaire. All patients 

who received at least 1 dose of study medication were 

included in the safety analyses. 

It was estimated that a sample size of 81 patients per 

treatment group was necessary to provide 90% power to 

detect a difference between the groups. In a crossover 

study, this means that 81 patients had to complete both 

treatments (triptorelin pamoate/leuprolide acetate). The 

target was a total of 100 patients enrolled to have at 

least 80 who would complete the study. All statistical 

comparisons for patient perceptions were conducted 

as two-sided tests, with p ≤ 0.05 considered statistically 

significant. Primary and secondary assessments were 

analyzed using an analysis of variance (ANOVA) model, 

adjusting for sequence, patient within sequence, period, 

and treatment. Clinician perception and safety data are 

summarized descriptively. 

results 

Patients 

A total of 118 patients were randomized, with 63 

randomized to receive triptorelin IM first and 55 to receive 

leuprolide SC first. Of the 107 patients who completed 

the study, 58 patients received triptorelin IM first and 49 

patients received leuprolide SC first. Demographic and 

physical characteristics of patients at baseline generally 

were similar between the two groups (Table 1). 

Patient Perceptions 

Patients reported significantly less post-injection burning 

and/or stinging with triptorelin IM than with leuprolide SC 

(p < 0.0001; Figure 1). In addition, significantly less postinjection 

soreness and less discomfort was reported with 

triptorelin IM than with leuprolide SC (both p < 0.0001; 

Figure 2). Results from other secondary assessments are 

reported in Table 2. Triptorelin IM versus leuprolide SC 

was associated with significantly less bother by redness, 

itching, and hardening (p ≤ 0.04), numerically less bother 

from bruising and swelling, and significantly greater 

satisfaction with overall injection experience (p = 0.0009). 

Significantly more anxiety prior to injection (p = 0.0271) 

and significantly more anxiety about a future injection 

with the same product (p = 0.0006) were reported with 

leuprolide SC than with triptorelin IM. 

Clinician Perceptions 

Clinicians reported less patient distress with triptorelin 

IM versus leuprolide SC (Figure 3). Clinicians also 

reported greater overall satisfaction with triptorelin IM 

Characteristic 

Age, y 

Mean (SD) 

Range 

Race, n (%) 

White 

African American 

Asian 

American Indian/Alaska Native 

Native Hawaiian/Pacific Islander 

Ethnicity, n (%) 

Hispanic or Latino 

Not Hispanic or Latino 

Previous GnRH therapy, n (%) 

Leuprolide (IM) 

Leuprolide (SC) 

Triptorelin 

Triptorelin First 

(n=58) 

73.2 (9.6) 

57-91 

44 (76) 

12 (21) 

1 (2) 

1 (2) 

0 

2 (3) 

56 (97) 

38 (66) 

9 (16) 

22 (38) 

7 (12) 

Leuprolide First 

(n=49) 

75.0 (9.6) 

56-91 

38 (78) 

10 (20) 

0 

0 

1 (2) 

3 (6) 

46 (94) 

31 (63) 

9 (18) 

18 (37) 

4 (8) 

Overall 

(N=107) 

74.0 (9.7) 

56-91 

82 (77) 

22 (21) 

1 (1) 

1 (1) 

1 (1) 

5 (5) 

102 (95) 

69 (64) 

18 (17) 

40 (37) 

11 (10) 

Height, cm 

Mean (SD) 176.9 (7.6) 174.8 (7.2) 175.9 (7.5) 

Weight, kg 

Mean (SD) 

Range 

89.5 (17.6) 

57.6–163 

89.9 (22.8) 

49.1–165 

–– 

Notes: GnRH = gonadotropin-releasing hormone, IM = intramuscular, SC = subcutaneous. 

Figure 1. Figure 2. 

How much were you bothered by burning and/or stinging How much discomfort did you 

experience from the injection 

Leuprolide 

Triptorelin 

Not bothered 

at all 

VAS Score 

Extremely 

bothered 

0 20 40 60 80 100 

Adjusted mean score indicating how much 

patients were bothered by burning and/or 

stinging on a VAS. 

Leuprolide 

Triptorelin 

No 

discomfort 

Worst 

discomfort 

0 20 40 60 80 100 

VAS Score 

89.7 (20.0) 

49.1–165 

How much were you bothered by soreness 

Leuprolide 

Triptorelin 

Not 

bothered 

at all 

Extremely 

bothered 

0 20 40 60 80 100 

VAS Score 

Adjusted mean scores indicating how much patients were bothered 

by soreness and how much discomfort patients experienced from the 

injection on a VAS. 

oncologistics 9

drug update 


Figure 3. 

In your opinion, how much distress do 

you think you patient experienced 

associated with this injection 

How satisfied are you overall with the 

injection experience 

Figure 4. 

I felt protected from accidental needle 

stickes following product administration 

The injection of the product was easy 

Leuprolide 

Leuprolide 

Leuprolide 

Leuprolide 

Triptorelin 

Triptorelin 

Triptorelin 

Triptorelin 

No distress 

at all 

Extremely 

distressed 

0 20 40 60 80 100 

VAS Score 

Completely 

satisfied 

Not satisfied 

at all 

0 20 40 60 80 100 

VAS Score 

Mean scores indicating how much distress 

clinicians thought patient experienced 

associated with the injection and clinicians’ 

overall satisfaction with the injection 

experience on a VAS. 

Strongly 

agree 

Strongly 

disagree 

0 20 40 60 80 100 

VAS Score 

Strongly 

agree 

Strongly 

disagree 

0 20 40 60 80 100 

VAS Score 

Mean scores indicating clinicians’ 

satisfaction with the injection process 

and device disposal on the VAS. 

Table 2: Results From Secondary Assessments of Patient Perceptions 


Characteristic 

Bother from redness 

Adjusted mean (95% CI) 

Range 

Bother from bruising 


Range 

Bother from itching 


Range 

Bother from hardening 


Range 

Bother from swelling 


Range 

Anxiety prior to injection 


Range 

Anxiety post-injection* 


Range 

Dissatisfaction with overall 

injection experience 


Range 

Triptorelin Injection 

(n=107) 

3.39 (1.57–5.22) 

0–28 

2.95 (1.12–4.77) 

0–31 

2.70 (1.49–3.91) 

0–17 

3.47 (1.62–5.31) 

0–34 

3.04 (1.41–4.68) 

0–18 

12.42 (7.38–17.46) 

0–99 

6.65 (2.11–11.19) 

0–94 

5.21 (1.47–8.96) 

0–91 

–– 

*Anxiety post-injection about getting another injection with the same product. 

Leuprolide Injection 

(n=107) 

6.26 (4.43–8.09) 

0–87 

4.90 (3.08–6.73) 

0–96 

5.14 (3.93–6.34) 

0–47 

6.16 (4.31–8.00) 

0–99 

5.01 (3.37–6.64) 

0–98 

19.05 (14.00–24.09) 

0–100 

17.27 (12.73–12.81) 

0–100 

13.44 (9.70–17.19) 

0–100 

Difference 

2.87 (0.28–5.45) 

p = 0.0302 

1.96 (-0.61–4.52) 

p = 0.1331 

2.43 (0.74–4.13) 

p = 0.0052 

2.69 (12.60–23.46) 

p = 0.0386 

1.96 (-0.29–4.21) 

p = 0.0869 

6.62 (0.76–12.48) 

p = 0.0271 

10.62 (4.68–16.56) 

p = 0.0006 

8.23 (3.47–12.99) 

p = 0.0009 

than leuprolide SC (Figure 3). In addition, clinicians reported 

more ease of injection with triptorelin IM versus leuprolide 

SC and felt more protected from accidental needle sticks 

after administering triptorelin versus leuprolide (Figure 4). 

Clinicians’ satisfaction assessments with other aspects of 

the study medications are reported in Table 3, with greater 

satisfaction with individual aspects reported with triptorelin 

versus leuprolide. 

Adverse Events 

Both study medications generally were well tolerated. 

Injection site pain was the most commonly reported AE and 

was reported by one patient in the triptorelin IM group and 

two patients in the leuprolide SC group. Other AEs reported 

were cystitis (1 patient in the triptorelin group), diarrhea (1 

patient in the leuprolide group), and urinary retention (1 

patient in the triptorelin group). 

Discussion 

In the present study, patients reported that triptorelin IM is 

associated with significantly less post-injection burning and/ 

or stinging than leuprolide SC. In addition, significantly less 

post-injection soreness, discomfort, bother by redness, 

itching, and hardening, and anxiety were reported with 

triptorelin IM versus leuprolide SC. Similarly, patients reported 

significantly greater satisfaction with triptorelin IM versus 

leuprolide SC. Clinicians reported greater overall satisfaction 

and lower perceived patient distress with triptorelin IM versus 

leuprolide SC, Clinicians also reported greater convenience, 

ease, and satisfaction for all questionnaire parameters, 

including injection setup, preparation, administration, and 

disposal with triptorelin IM versus leuprolide SC. Both 

treatments were well tolerated. 

The efficacy and tolerability of triptorelin pamoate IM and 

leuprolide acetate SC in patients with advanced prostate 

cancer have been previously established (Sanofi-Aventis 

US, LLC, 2011; Watson Pharma, Inc., 2001). An earlier 

parallel-group, randomized, controlled multicenter study 

compared the efficacy and tolerability of triptorelin pamoate 

with leuprolide acetate in 284 men with advanced cancer 

(Heyns et al., 2003). Notably, however, both medications in 

the study were administered intramuscularly (Heyns et al., 

2003). Findings from the study showed that triptorelin and 

leuprolide were both effective in maintaining castration and 

had similar tolerability (Heyns et al., 2003). When there is 

comparable efficacy between treatment options, a patient’s 

preference should be considered when making decisions 

about treatments (Wennberg, 2002). 

Understanding individual patients’ preferences for 

medications is important in clinical practice (Blinman, King, 

Norman, Viney, & Stockler, 2012). It allows physicians to 

tailor cancer treatments to individual patients (Blinman et al., 

2012). Moreover, patient preferences for a medication can 

oncologistics 11

drug update 


Table 3: Clinicians’ Satisfaction With Various Aspects of the Study Medications 


Characteristic Triptorelin Injection Leuprolide Injection 

Time required to administer the 

product was reasonable 

Mean (SD) 

Range 

Convenience of storage before 

administration 

Mean (SD) 

Range 

Instructions simple and easy to 

understand 

Mean (SD) 

Range 

All components of injection device 

were easy to identify 

Mean (SD) 

Range 

Time required to setup for the 

injection was reasonable 

Mean (SD) 

Range 

It was easy to prepare the device 

before injection 

Mean (SD) 

Range 

The product was easy to mix using 

the device 

Mean (SD) 

Range 

It was easy to draw the product 

into the syringe and attach to 

the needle 

Mean (SD) 

Range 

Time required to prepare the 

product was reasonable 

Mean (SD) 

Range 

5.32 (12.47) 

0–98 

3.59 (9.61) 

0–83 

5.04 (10.53) 

0–76 

4.27 (9.48) 

0–79 

4.41 (8.92) 

0–71 

5.29 (10.18) 

0–78 

6.21 (12.46) 

0–80 

7.54 (13.83) 

0–78 

4.88 (9.16) 

0–75 

15.56 (17.67) 

0–60 

10.72 (15.6) 

0–88 

9.73 (13.24) 

0–77 

11.17 (16.9) 

0–97 

12.47 (16.94) 

0–94 

13.16 (16.72) 

0–94 

15.45 (17.99) 

0–93 

19.0 (20.28) 

0–81 

16.88 (19.36) 

0–86 

affect treatment compliance, and consequently, treatment 

outcomes (Cameron, 1996). Treatment tolerability, complexity 

and convenience of treatment regimen, and the duration 

of treatment also affect patient compliance with treatment 

(Anderson, 2003; Cameron, 1996). Additional studies to further 

assess perceptions of GnRH agonists and the 

effect of these perceptions on treatment compliance are 

warranted to identify medication factors that could potentially 

improve compliance. 

Using VAS questionnaires, this study provided important 

information about patients’ and clinicians’ perceptions of two 

different GnRH agonist therapies. The VAS questionnaire is 

an easy and convenient tool that can be rapidly completed 

by patients or clinicians (Torrance, Feeny, & Furlong, 2001; 

Wewers & Lowe, 1990). However, there are limitations to 

findings obtained with VAS assessments. One limitation is 

measurement bias; people tend to avoid choosing the extreme 

ends of a continuous scale (Blinman et al., 2012). Comparability 

of scores between respondents also is limited (Blinman et al., 

2012), because the VAS is subjective in nature and based on 

personal perceptions (Wewers et al., 1990). Moreover, some 

patients may not conceptually understand the VAS, which 

has been noted with elderly patients (Wewers et al., 1990). An 

additional limitation of the study is that AEs were evaluated for 

only 24 hours after administration of study medication. Certain 

longer-term AEs would not have been captured in this study. A 

future study assessing AEs for at least 72 hours post-injection 

would further describe the tolerability of GnRH agonists. 

Despite the study’s limitations, the present findings provide 

important information regarding patients’ perceptions 

of triptorelin IM versus leuprolide SC. The differences in 

perceptions between these medications may be attributable 

to the different routes of administration. In general, advantages 

of SC injections include a greater area for target injection sites 

and injections can be more easily self-administered (Prettyman, 

2005). In addition, the patient’s muscle mass does not need to 

be considered, and SC injections generally have a better safety 

profile (Prettyman, 2005). On the other hand, IM injections 

allow for a greater volume of medication to be delivered, and 

medications that are irritating to SC tissues may be less so 

when administered intramuscularly (Prettyman, 2005). 

Findings from the present study suggest that patients may 

prefer the IM GnRH agonist injection over the SC injection. 

Few studies of patients’ preferences for IM or SC injections 

have been published. To our knowledge, perceptions of 

the tolerability of GnRH agonists have not been previously 

evaluated. However, results from a study conducted in patients 

with diabetes demonstrated that seven out of eight patients 

reported equal pain when injecting insulin IM versus SC (Vaag, 

Pedersen, Lauritzen, Hildebrandt, & Beck-Nielsen, 1990). 

Findings from a previous randomized, open-label, parallelgroup 

study of 620 men with prostate cancer suggest that 

SC injections may be associated with more frequent injectionsite 

reactions than IM injections (Klotz et al., 2008). In the 

study, 40% of patients given SC degarelix, a GnRH receptor 

antagonist, reported injection-site reactions, compared with 


drug update 

studies are needed to better understand how the route of 

administration affects patients’ and clinicians’ preferences 

for medications. 

Conclusion 

Triptorelin IM and leuprolide SC were both well tolerated, 

but patients reported less post-injection burning and/ 

or stinging, soreness, discomfort, and anxiety with 

triptorelin IM versus leuprolide SC. Similarly, clinicians 

reported greater overall satisfaction, convenience, 

ease, as well as greater patient satisfaction and lower 

perceived patient distress with triptorelin IM versus 

leuprolide SC. Although the present study had limitations, 

many inherent to the limitations of VAS questionnaires 

in general, it is the first study to provide important 

information regarding preference for GnRH agonists. 

Future studies are warranted to further determine factors 

that may contribute to and affect patient preferences and 

treatment compliance. 

ACknowledgement 

Anny Wu, PharmD, Marsha Hall, BA, and Matthew 

Dougherty, BA (Scientific Connexions, Newtown, PA) 

provided medical writing and editorial assistance, 

supported by Watson Pharma, Inc. 

Neal D. Shore, MD, FACS, is managing partner, 

Atlantic Urology Clinics and Director, CPI, the Carolina 

Urologic Research Center, Myrtle Beach, SC. 

Paul Sieber, MD, FACS, is a urologist, Lancaster 

Urology, Lancaster, PA. 

Leanne Schimke, MSN, CRNP, FNP-C, CUNP, is a 

nurse practitioner, Lancaster Urology, Lancaster, PA. 

Adam Perzin, MD, is president of Delaware Valley 

Urology, Voorhees, NJ. 

Scott Olsen, MPH, is associate director, Clinical 

Affairs, Watson Pharmaceuticals, Salt Lake City, UT. 

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11. Torrance, G.W., Feeny, D., & Furlong, W. (2001). Visual Analog 

Scales: do they have a role in the measurement of preferences 

for health states Med Decis Making 21(4), 329-334. doi. 

org/10.1177/0272989X0102100408 

12. vaag, A., Pedersen, K.D., Lauritzen, M., Hildebrandt, P., & Beck- 

Nielsen, H. (1990). Intramuscular versus subcutaneous injection 

of unmodified insulin: consequences for blood glucose control in 

patients with type 1 diabetes mellitus. Diabet Med 7(4), 335-442. 

doi.org/10.1111/j.1464-5491.1990.tb01401.x 

13. Watson Pharma, Inc. (2001). Trelstar: Highlights of prescribing 

information. Available at: http://pi.watson.com/data_stream. 

aspproduct_group=1684&p=pi&language=E. Accessed 

September 4, 2012. 

14. Wennberg, J.E. (2002). Unwarranted variations in healthcare 

delivery: implications for academic medical centres. BMJ 325(7370), 

961-964. doi.org/ 10.1136/bmj.325.7370.961 

15. Wewers, M.E., & Lowe, N.K. (1990). A critical review of visual 

analogue scales in the measurement of clinical phenomena. Res 

Nurse Health 13(4), 227-236. doi.org/10.1002/nur.4770130405 

In Men With Advanced Prostate Cancer 

DEPENDABLE TESTOSTERONE 

SUPPRESSION 

Few castration escapes with 

Trelstar® therapy occurred 

during months 2 to 9 1,2 * 

• 4 patients (5 occurrences) in the 

Trelstar® 3.75 mg group 

• 11 patients (18 occurrences) in the 

active comparator group 

Convenient, well-tolerated delivery 

• Simple IM injection with MIXJECT®— 

no refrigeration necessary 

• Well-tolerated IM administration—injection 

site pain occurred in 2 patients (1.7%) 

with Trelstar® 22.5 mg (N=120) 3 

• Trelstar® is available for 1-month 

(3.75 mg), 3-month (11.25 mg), and 

6-month (22.5 mg) administration 

Mean Testoster 

stosterone one Level (ng/dL) 

50 

20 

Trelsta 

elstar ® 3.75 mg (n=137) † 

Active comparator (n=140) † 

50 ng/dL castrate level 

0 

29 57 85 113 141 169 197 

225 253 

Days 

Based on a 9-month, multicenter, parallel group, blindly randomized, controlled 

clinical trial comparing Trelstar® 3.75 mg to an active comparator in patients 

with advanced (stage C/D) prostate cancer (N=284). Mean testosterone 

concentrations were calculated from months 2 through 9. 

* The clinical benefi ts of maintaining testosterone levels


BRIEF SUMMARY 

For full Prescribing Information, see package insert. 

INDICATIONS AND USAGE 

TRELSTAR is indicated for the palliative treatment of advanced prostate cancer. 

CONTRAINDICATIONS 

Hypersensitivity 

TRELSTAR is contraindicated in individuals with a known hypersensitivity to triptorelin or 

any other component of the product, or other GnRH agonists or GnRH [see Warnings and 

Precautions]. 

Pregnancy 

TRELSTAR may cause fetal harm when administered to a pregnant woman. Expected hormonal 

changes that occur with TRELSTAR treatment increase the risk for pregnancy loss and fetal 

harm when administered to a pregnant woman [see Use in Specific Populations]. TRELSTAR 

is contraindicated in women who are or may become pregnant. If this drug is used during 

pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be 

apprised of the potential hazard to the fetus. 

WARNINGS AND PRECAUTIONS 

Hypersensitivity Reactions 

Anaphylactic shock, hypersensitivity, and angioedema related to triptorelin administration 

have been reported. In the event of a hypersensitivity reaction, therapy with TRELSTAR 

should be discontinued immediately and the appropriate supportive and symptomatic care 

should be administered. 

Transient Increase in Serum Testosterone 

Initially, triptorelin, like other GnRH agonists, causes a transient increase in serum testosterone 

levels. As a result, isolated cases of worsening of signs and symptoms of prostate 

cancer during the first weeks of treatment have been reported with GnRH agonists. Patients 

may experience worsening of symptoms or onset of new symptoms, including bone pain, 

neuropathy, hematuria, or urethral or bladder outlet obstruction. 

Metastatic Vertebral Lesions and Urinary Tract Obstruction 

Cases of spinal cord compression, which may contribute to weakness or paralysis with 

or without fatal complications, have been reported with GnRH agonists. If spinal cord 

compression or renal impairment develops, standard treatment of these complications 

should be instituted, and in extreme cases an immediate orchiectomy considered. 

Patients with metastatic vertebral lesions and/or with upper or lower urinary tract obstruction 

should be closely observed during the first few weeks of therapy. 

Hyperglycemia and Diabetes 

Hyperglycemia and an increased risk of developing diabetes have been reported in men receiving 

GnRH agonists. Hyperglycemia may represent development of diabetes mellitus or worsening 

of glycemic control in patients with diabetes. Monitor blood glucose and/or glycosylated 

hemoglobin (HbA1c) periodically in patients receiving a GnRH agonist and manage with current 

practice for treatment of hyperglycemia or diabetes. 

Cardiovascular Diseases 

Increased risk of developing myocardial infarction, sudden cardiac death and stroke has been 

reported in association with use of GnRH agonists in men. The risk appears low based on 

the reported odds ratios, and should be evaluated carefully along with cardiovascular risk 

factors when determining a treatment for patients with prostate cancer. Patients receiving a 

GnRH agonist should be monitored for symptoms and signs suggestive of development of 

cardiovascular disease and be managed according to current clinical practice. 

Laboratory Tests 

Response to TRELSTAR should be monitored by measuring serum levels of testosterone 

periodically or as indicated. 

Laboratory Test Interactions 

Chronic or continuous administration of triptorelin in therapeutic doses results in suppression 

of pituitary-gonadal axis. Diagnostic tests of the pituitary-gonadal function conducted during 

treatment and after cessation of therapy may therefore be misleading. 

ADVERSE REACTIONS 

Clinical Trials Experience 

Because clinical trials are conducted under widely varying conditions, adverse reaction rates 

observed in the clinical trials of a drug cannot be directly compared with rates in the clinical 

trials of another drug and may not reflect the rates observed in practice. 

The safety of the three TRELSTAR formulations was evaluated in clinical trials involving 

patients with advanced prostate cancer. Mean testosterone levels increased above baseline 

during the first week following the initial injection, declining thereafter to baseline levels or 

below by the end of the second week of treatment. The transient increase in testosterone levels 

may be associated with temporary worsening of disease signs and symptoms, including bone 

pain, neuropathy, hematuria, and urethral or bladder outlet obstruction. Isolated cases of 

spinal cord compression with weakness or paralysis of the lower extremities have occurred 

[see Warnings and Precautions]. 

Adverse reactions reported for each of the three TRELSTAR formulations in the clinical trials, are 

presented in Table 2, Table 3, and Table 4. Often, causality is difficult to assess in patients with 

metastatic prostate cancer. The majority of adverse reactions related to triptorelin are a result 

of its pharmacological action, i.e., the induced variation in serum testosterone levels, either 

an increase in testosterone at the initiation of treatment, or a decrease in testosterone once 

castration is achieved. Local reactions at the injection site or allergic reactions may occur. 

The following adverse reactions were reported to have a possible or probable relationship 

to therapy as ascribed by the treating physician in at least 1% of patients receiving 

Trelstar 3.75 mg. 

Table 2. TRELSTAR 3.75 mg: Treatment-Related Adverse Reactions Reported 

by 1% or More of Patients During Treatment 

TRELSTAR 3.75 mg 

N = 140 

Adverse Reactions 1 

N % 

Application Site Disorders 

Injection site pain 5 3.6 

Body as a Whole 

Hot flush 

Pain 

Leg pain 

Fatigue 

82 

3 

3 

3 

58.6 

2.1 

2.1 

2.1 

Cardiovascular Disorders 

Hypertension 5 3.6 

Central and Peripheral Nervous System Disorders 

Headache 

Dizziness 

Gastrointestinal Disorders 

Diarrhea 

Vomiting 

7 

2 

2 

3 

5.0 

1.4 

1.4 

2.1 

Musculoskeletal System Disorders 

Skeletal pain 17 12.1 

Psychiatric Disorders 

Insomnia 

Impotence 

Emotional lability 

3 

10 

2 

2.1 

7.1 

1.4 

Red Blood Cell Disorders 

Anemia 2 1.4 

Skin and Appendages Disorders 

Pruritus 2 1.4 

Urinary System Disorders 

Urinary tract infection 

Urinary retention 

2 

2 

1.4 

1.4 

1 Adverse reactions for TRELSTAR 3.75 mg are coded using the WHO Adverse Reactions 

Terminology (WHOART) 

The following adverse reactions were reported to have a possible or probable relationship 

to therapy as ascribed by the treating physician in at least 1% of patients receiving 

Trelstar 11.25 mg. 

Table 3. TRELSTAR 11.25 mg: Treatment-Related Adverse Reactions 

Reported by 1% or More of Patients During Treatment 


N = 174 


N % 

Application Site 

Injection site pain 7 4.0 

Body as a Whole 

Hot flush 

Leg pain 

Pain 

Back pain 

Fatigue 

Chest pain 

Asthenia 

Peripheral edema 

Cardiovascular Disorders 

Hypertension 

Dependent edema 

Central and Peripheral Nervous System Disorders 

Headache 

Dizziness 

Leg cramps 

Endocrine 

Breast pain 

Gynecomastia 

Gastrointestinal Disorders 

Nausea 

Constipation 

Dyspepsia 

Diarrhea 

Abdominal pain 

127 

9 

6 

5 

4 

3 

2 

2 

7 

4 

12 

5 

3 

4 

3 

5 

3 

3 

2 

2 

73.0 

5.2 

3.4 

2.9 

2.3 

1.7 

1.1 

1.1 

4.0 

2.3 

6.9 

2.9 

1.7 

2.3 

1.7 

2.9 

1.7 

1.7 

1.1 

1.1 

Liver and Biliary System 

Abnormal hepatic function 2 1.1 

Metabolic and Nutritional Disorders 

Edema in legs 

Increased alkaline phosphatase 

Musculoskeletal System Disorders 

Skeletal pain 

Arthralgia 

Myalgia 


Decreased libido 

Impotence 

Insomnia 

Anorexia 

Respiratory System Disorders 

Coughing 

Dyspnea 

Pharyngitis 

11 

3 

23 

4 

2 

4 

4 

3 

3 

3 

2 

2 

6.3 

1.7 

13.2 

2.3 

1.1 

2.3 

2.3 

1.7 

1.7 

1.7 

1.1 

1.1 

Skin and Appendages 

Rash 3 1.7 

Urinary System Disorders 

Dysuria 


Vision Disorders 

Eye pain 

Conjunctivitis 

1 Adverse reactions for TRELSTAR 11.25 mg are coded using the WHO Adverse Reactions 

Terminology (WHOART) 

The following adverse reactions occurred in at least 5% of patients receiving TRELSTAR 22.5 

mg. The table includes all reactions whether or not they were ascribed to TRELSTAR by the 

treating physician. The table also includes the incidence of these adverse reactions that were 

considered by the treating physician to have a reasonable causal relationship or for which the 

relationship could not be assessed. 

Table 4. TRELSTAR 22.5 mg: Adverse Reactions Reported by 5% or More of 

Patients During Treatment 

8 

2 

2 

2 

4.6 

1.1 

1.1 

1.1 


N = 120 

Treatment-Emergent Treatment-Related 


N % N % 

General Disorders and 

Administration Site Conditions 

Edema peripheral 6 5.0 0 0 

Infections and Infestations 

Influenza 

Bronchitis 

19 

6 

15.8 

5.0 

Endocrine 

Diabetes Mellitus/Hyperglycemia 6 5.0 0 0 

Musculoskeletal and Connective 

Tissue Disorders 

Back pain 

Arthralgia 

Pain in extremity 

13 

9 

9 

10.8 

7.5 

7.5 

0 

0 

1 

1 

1 

0 

0 

0.8 

0.8 

0.8 

Nervous System Disorders 

Headache 9 7.5 2 1.7 


Insomnia 6 5.0 1 0.8 

Renal and Urinary Disorders 

Urinary tract infection 


Reproductive System and 

Breast Disorders 

Erectile dysfunction 

Testicular atrophy 

Vascular Disorders 

Hot flush 

Hypertension 

14 

6 

12 

9 

87 

17 

11.6 

5.0 

10.0 

7.5 

72.5 

14.2 

1 Adverse reactions for TRELSTAR 22.5 mg are coded using the Medical Dictionary for 

Regulatory Activities (MedDRA) 

0 

0 

12 

9 

86 

1 

0 

0 

10.0 

7.5 

71.7 

0.8 

Changes in Laboratory Values During Treatment 

The following abnormalities in laboratory values not present at baseline were observed in 10% 

or more of patients: 

TRELSTAR 3.75 mg: There were no clinically meaningful changes in laboratory values 

detected during therapy. 

TRELSTAR 11.25 mg: Decreased hemoglobin and RBC count and increased glucose, BUN, 

SGOT, SGPT, and alkaline phosphatase at the Day 253 visit. 

TRELSTAR 22.5 mg: Decreased hemoglobin and increased glucose and hepatic transaminases 

were detected during the study. The majority of the changes were mild to moderate. 

Postmarketing Experience 

The following adverse reaction has been identified during post approval use of gonadotropin 

releasing hormone agonists. Because this reaction is recorded voluntarily from a population of 

uncertain size, it is not always possible to reliably estimate its frequency or establish a causal 

relationship to drug exposure. 

During postmarketing surveillance, rare cases of pituitary apoplexy (a clinical syndrome 

secondary to infarction of the pituitary gland) have been reported after the administration of 

gonadotropin-releasing hormone agonists. In a majority of these cases, a pituitary adenoma 

was diagnosed with a majority of pituitary apoplexy cases occurring within 2 weeks of the first 

dose, and some within the first hour. In these cases, pituitary apoplexy has presented as sudden 

headache, vomiting, visual changes, ophthalmoplegia, altered mental status, and sometimes 

cardiovascular collapse. Immediate medical attention has been required. 

DRUG INTERACTIONS 

No drug-drug interaction studies involving triptorelin have been conducted. 

Human pharmacokinetic data with triptorelin suggest that C-terminal fragments produced by 

tissue degradation are either degraded completely within tissues or are rapidly degraded further 

in plasma, or cleared by the kidneys. Therefore, hepatic microsomal enzymes are unlikely 

to be involved in triptorelin metabolism. However, in the absence of relevant data and as a 

precaution, hyperprolactinemic drugs should not be used concomitantly with triptorelin since 

hyperprolactinemia reduces the number of pituitary GnRH receptors. 

USE IN SPECIFIC POPULATIONS 

Pregnancy 

Pregnancy Category X [see ‘Contraindications’ section]. 

TRELSTAR is contraindicated in women who are or may become pregnant while receiving the 

drug. Expected hormonal changes that occur with TRELSTAR treatment increase the risk for 

pregnancy loss. If this drug is used during pregnancy, or if the patient becomes pregnant while 

taking this drug, the patient should be apprised of the potential hazard to the fetus. 

Studies in pregnant rats administered triptorelin at doses of 2, 10, and 100 mcg/kg/day 

(approximately equivalent to 0.2, 0.8, and 8 times the estimated human daily dose based on 

body surface area) during the period of organogenesis demonstrated maternal toxicity and 

embryo-fetal toxicities. Embryo-fetal toxicities consisted of pre-implantation loss, increased 

resorption, and reduced mean number of viable fetuses at the high dose. Teratogenic effects 

were not observed in viable fetuses in rats or mice. Doses administered to mice were 2, 20, 

and 200 mcg/kg/day (approximately equivalent to 0.1, 0.7, and 7 times the estimated human 

daily dose based on body surface area). 

Nursing Mothers 

TRELSTAR is not indicated for use in women [see Indications and Usage]. It is not known if 

triptorelin is excreted in human milk. Because many drugs are excreted in human milk, and 

because of the potential for serious adverse reactions in nursing infants from TRELSTAR, a 

decision should be made to either discontinue nursing, or discontinue the drug taking into 

account the importance of the drug to the mother. 

Pediatric Use 

Safety and effectiveness in pediatric patients have not been established. 

Geriatric Use 

Prostate cancer occurs primarily in an older population. Clinical studies with TRELSTAR have 

been conducted primarily in patients ≥ 65 years. 

Renal Impairment 

Subjects with renal impairment had higher exposure than young healthy males. 

Hepatic Impairment 

Subjects with hepatic impairment had higher exposure than young healthy males. 

OVERDOSAGE 

There is no experience of overdosage in clinical trials. In single dose toxicity studies in 

mice and rats, the subcutaneous LD 50 of triptorelin was 400 mg/kg in mice and 250 mg/kg 

in rats, approximately 500 and 600 times, respectively, the estimated monthly human 

dose based on body surface area. If overdosage occurs, therapy should be discontinued 

immediately and the appropriate supportive and symptomatic treatment administered. 

Distributed By: Watson Pharma, Inc., Parsippany, NJ 07054 USA 

Manufactured By: Debio RP, CH-1920 Martigny, Switzerland 

For all medical inquiries contact: WATSON Medical Communications, Parsippany, NJ 

07054 800-272-5525 

MIXJECT is manufactured by and is a registered trademark of: Medimop Medical Projects 

Ltd., Ra’anana, Israel 

The pre-filled syringe containing sterile water for injection is manufactured by: Solvay 

Biologicals BV, Olst, The Netherlands 

Rx only Revised: March 2011 

oncologistics 17

industry insight 

oncologistics industry insight 

WHY CommuniTY 

Counts 

By: Chris Vorce 

Community oncology has long been a key component in this nation’s healthcare delivery system. 

Despite the implementation of the Medicare Modernization Act, and other measures that have cut 

reimbursement and made it more difficult for private practices to operate, community oncologists 

continue to treat the majority of patients in the United States. The community oncology model was 

essentially created to remove cancer care from the hospital system, where treatments could be 

delivered conveniently, directly, efficiently, and at less cost to the patient. Unfortunately, over the 

years, Medicare reimbursement cuts have jeopardized this care delivery model. Furthermore, recently 

introduced sequestration cuts may push community oncology over the edge, and initiate a major 

regression in the way care is currently delivered to patients with cancer. 

In response to the changing dynamics of the 

These resources can be accessed on 

healthcare landscape, and to combat industry 

www.ourcommunitycounts.org, and include: 

forces that are effectively weakening community 

oncology, ION Solutions has launched the 

> Two educational Web cast series that provide 

Community Counts campaign. 

insight on how to become more efficient and 

grow/expand business 

This campaign aims to educate providers, payers, 

> Informative white papers that quantify the value 


and legislators on the issues that are affecting the 

viability of community oncology: the above-mentioned 

sequestration cuts, SGR cuts, the Affordable Care Act, 

etc; provide tools and resources to empower physicians 

to be able to advocate on their own behalf; and use 

ion Solutions’ standing in the market to amplify the 

voice of community oncology throughout the nation. 

of community oncology and can be used as the 

basis for discussions with legislators, payers, 

and others 

> Archival information on past events: live meetings, 

web casts, etc on sequestration 

> Site of Care presentation deck, to arm practices 

with insight needed to conduct meaningful 

discussions with payers and legislators 

In response to the changing dynAMiCS of the healTHCARe 

lanDSCApe, and to combAT inDUSTRY foRCes that are eFFeCTively 

weakening communiTY oncoloGY, ION SolUTions has lAUnCHed 

THe CommuniTY CounTS campaign. 

oncologistics 19


> Several practice efficiency resources: “9 Habits 

of a Healthy Practice”, survey results, editorials, 

talking points 

> Patient-facing materials: waiting room posters, call 

to action letters, talking points, etc 

> An advocacy tool that allows practice personnel to 

contact regional legislators in an effort to combat 

recent sequestration cuts 

ion Solutions truly believes that the community setting 

provides the best opportunity for convenient, efficient, 

and effective cancer care. We are wholly committed 

to this space, and will continue to dedicate our time, 

energy, and resources to supporting your mission of 

providing optimal patient care. As sequestration cuts 

begin to influence the way that you are able to treat your 

patients and serve your community, please let us know 

what we can provide to help. 

Contact your ION Solutions strategic account manager, 

or visit www.ourcommunitycounts.org to learn more. 

The future of your practice 

begins here and now. 


Chris Vorce is director, marketing and communications, 

at ION Solutions. 

Share your voice with legislators at 

CommunityCountsAdvocacy.org 

It’s time to demonstrate the real, measurable 

value of community oncology. 

To ensure the future of community oncology, we must communicate its value today. 

Community Counts is a physician-led movement that puts the power in your hands. 

Simply register at ourcommunitycounts.org and gain access to information and tools 

to help you learn how to navigate this new healthcare environment, and operate 

more efficiently in it. 

So join the cause and make your voice count. Go to ourcommunitycounts.org today.

2013 Meeting Schedule 

For melanoma patients with microscopic 

or gross nodal involvement 

Meeting Date Meeting Name Location Venue 

April 19-21, 2013 LPP National Meeting Washington, DC Renaissance 

May 17-19, 2013 Business of Oncology Washington, DC Renaissance 

Sept 20-22, 2013 National Healthcare Nashville, TN Loews Vanderbilt 

Practitioners Meeting 

Sept 27-29, 2013 LPP Select Meeting Dallas, TX Fairmont Dallas 

Oct 25-27, 2013 LPP Excel Meeting Dallas, TX Dallas Marriott 

City Center 

November 8-10, 2013 ION National Meeting Phoenix, AZ Sheraton Downtown 

A Perspective on Adjuvant Therapy 

Significant effect on 

relapse-free survival 

Based on 696 relapse-free survival (RFS) events, determined by the Independent Review Committee, 

median RFS was 34.8 months (95% CI, 26.1–47.4) and 25.5 months (95% CI, 19.6–30.8) in the group 

treated with SYLATRON (peginterferon alfa-2b) and the observation group, respectively. The estimated 

hazard ratio for RFS was 0.82 (95% CI, 0.71–0.96; unstratified log-rank P=0.011) in favor of SYLATRON. 

SYLATRON is indicated for the adjuvant treatment of melanoma with microscopic or gross nodal 

involvement within 84 days of definitive surgical resection including complete lymphadenectomy. 

SELECT IMPORTANT SAFETY INFORMATION 

WARNING: Depression and other Neuropsychiatric Disorders 

The risk of serious depression, with suicidal ideation and completed suicides, and other 

serious neuropsychiatric disorders are increased with alpha interferons, including SYLATRON. 

Permanently discontinue SYLATRON in patients with persistently severe or worsening signs 

or symptoms of depression, psychosis, or encephalopathy. These disorders may not resolve 

after stopping SYLATRON. 

SYLATRON is contraindicated in patients with a history of anaphylaxis to peginterferon alfa-2b or 

interferon alfa-2b, in patients with autoimmune hepatitis, and in patients with hepatic decompensation 

(Child-Pugh score >6 [Class B and C]). 

*Meeting dates subject to change* 

Please see the adjacent Brief Summary of the Prescribing Information, 

including the Boxed Warning about depression and other 

neuropsychiatric disorders. 

oncologistics 23


• Peginterferon alfa-2b can cause life-threatening or fatal neuropsychiatric reactions. These 

include suicide, suicidal and homicidal ideation, depression, and an increased risk of relapse 

of recovering drug addicts. Depression occurred in 59% of patients treated with SYLATRON 

(peginterferon alfa-2b) and 24% of patients in the observation group. Depression was severe 

or life-threatening in 7% of patients treated with SYLATRON compared with

SYLATRON (peginterferon alfa-2b) is indicated for the adjuvant treatment of melanoma 

with microscopic or gross nodal involvement within 84 days of definitive surgical resection 

including complete lymphadenectomy. 

A Perspective on Adjuvant Therapy 

Significant effect on 

relapse-free survival 

• In the pivotal study, the dose of SYLATRON was adjusted to maintain an ECOG Performance Status of 0 or 1. 

• Median duration of therapy: 

– 6-mcg/kg/wk dose: median 8.0 weeks 

– 3-mcg/kg/wk dose: median 14.3 months 

• Patients achieved a significant improvement in relapse-free survival. 

– Based on 696 RFS events, determined by the Independent Review Committee. 

– Median RFS was 34.8 months (95% CI, 26.1–47.4) and 25.5 months (95% CI, 19.6–30.8) in the group 

treated with SYLATRON and the observation group, respectively. 

– The estimated hazard ratio for RFS was 0.82 (95% CI, 0.71–0.96; unstratified log-rank P=0.011) 

in favor of SYLATRON. 


• There are no adequate and well-controlled studies of SYLATRON in pregnant women. Use SYLATRON 

during pregnancy only if the potential benefit justifies the potential risk to the fetus. 

• It is not known whether the components of SYLATRON are excreted in human milk. Because of the 

potential for adverse reactions from the drug in nursing infants, a decision must be made whether to 

discontinue nursing or discontinue treatment with SYLATRON. 

• Safety and effectiveness in patients below the age of 18 years have not been established. 

• Increase frequency of monitoring for SYLATRON toxicity in patients with moderate and severe renal impairment. 

Please see the adjacent Brief Summary of the Prescribing Information, 

including the Boxed Warning about depression and other neuropsychiatric disorders. 

Copyright © 2012 Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc. 

All rights reserved. ONCO-1064624-0000 12/12 

Brief Summary of the Prescribing Information 

WARNING: DEPRESSION AND OTHER NEUROPSYCHIATRIC DISORDERS 

The risk of serious depression, with suicidal ideation and completed suicides, 

and other serious neuropsychiatric disorders are increased with alpha interferons, 

including SYLATRON. Permanently discontinue SYLATRON in patients with 

persistently severe or worsening signs or symptoms of depression, psychosis, or 

encephalopathy. These disorders may not resolve after stopping SYLATRON 

[see Warnings and Precautions and Adverse Reactions]. 

INDICATIONS AND USAGE 

SYLATRON is an alpha interferon indicated for the adjuvant treatment of melanoma with 

microscopic or gross nodal involvement within 84 days of definitive surgical resection including 

complete lymphadenectomy. 

CONTRAINDICATIONS 

SYLATRON is contraindicated in patients with a history of anaphylaxis to peginterferon alfa-2b 

or interferon alfa-2b, autoimmune hepatitis, or hepatic decompensation (Child-Pugh score >6 [class 

B and C]). 

WARNINGS AND PRECAUTIONS 

Depression and Other Serious Neuropsychiatric Adverse Reactions 

Peginterferon alfa-2b can cause life-threatening or fatal neuropsychiatric reactions. These include 

suicide, suicidal and homicidal ideation, depression, and an increased risk of relapse of recovering 

drug addicts. In the clinical trial, depression occurred in 59% of SYLATRON-treated patients and 

24% of patients in the observation group. Depression was severe or life threatening in 7% of 

SYLATRON-treated patients compared with

Brief Summary of the Prescribing Information for SYLATRON (peginterferon alfa-2b) 

Immunogenicity 

As with all therapeutic proteins, there is potential for immunogenicity. The incidence of antibodies 

to peginterferon alfa-2b has not been studied in patients with melanoma. In clinical studies 

conducted in patients with chronic hepatitis C, the incidence of binding antibodies to peginterferon 

alfa-2b was approximately 10% (174/1,759). Among the patients tested positive for binding 

antibodies, 18% (32/174) developed neutralizing antibodies. 

The incidence of antibody formation is highly dependent on the sensitivity and specificity of the 

assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity 

in an assay may be influenced by several factors, including assay methodology, sample handling, 

timing of sample collection, concomitant medications, and underlying disease. For these reasons, 

comparison of the incidence of antibodies to SYLATRON with the incidence of antibodies to other 

products may be misleading. 

Postmarketing Experience 

The following adverse reactions have been identified during postapproval use of peginterferon 

alfa-2b as monotherapy and in combination with ribavirin in chronic hepatitis C (CHC) patients. 

Because these reactions are reported voluntarily from a population of uncertain size, it is not 

always possible to reliably estimate their frequency or establish a causal relationship to drug 

exposure. 

Blood and Lymphatic System Disorders: pure red cell aplasia, thrombotic thrombocytopenic 

purpura 

Ear and Labyrinth Disorders: hearing loss, vertigo, hearing impairment 

Endocrine Disorders: diabetic ketoacidosis 

Eye Disorders: Vogt-Koyanagi-Harada syndrome 

Gastrointestinal Disorders: aphthous stomatitis, pancreatitis, colitis 

Infusion reactions: angioedema, urticaria, bronchoconstriction 

Immune System Disorders: systemic lupus erythematosus, erythema multiforme, thyroiditis, 

thrombotic thrombocytopenic purpura, idiopathic thrombocytopenic purpura, rheumatoid arthritis, 

interstitial nephritis, and systemic lupus erythematosus 

Infections: sepsis 

Metabolism and Nutrition Disorders: hypertriglyceridemia 

Musculoskeletal and Connective Tissue Disorders: rhabdomyolysis, myositis 

Nervous System Disorders: seizures, memory loss, peripheral neuropathy, paraesthesia, 

migraine headache 

Respiratory, Thoracic, and Mediastinal Disorders: dyspnea, pulmonary infiltrates, pneumonia, 

bronchiolitis obliterans, interstitial pneumonitis, sarcoidosis, and pulmonary hypertension 

Skin and Subcutaneous Tissue Disorders: Stevens-Johnson syndrome, toxic epidermal 

necrolysis, psoriasis 

Vascular Disorders: hypertension, hypotension, stroke 

DRUG INTERACTIONS 

In healthy subjects who were administered peginterferon alfa-2b subcutaneously at 1 mcg/kg once 

weekly for four weeks with probe drugs of metabolic enzymes administered before the first dose 

and after the fourth dose, a measure of CYP2C9 activity increased to 125% of baseline, whereas a 

measure of CYP2D6 activity decreased to 51% of baseline. 

When administering SYLATRON with medications metabolized by CYP2C9 or CYP2D6, the 

therapeutic effect of these drugs may be altered. 

The effects of pegylated interferon alfa-2b on the pharmacokinetics of drugs metabolized by 

cytochrome P-450 enzymes have not been studied at the higher clinical doses for patients with 

melanoma (3 mcg/kg/week and 6 mcg/kg/week). 

USE IN SPECIFIC POPULATIONS 

Pregnancy 

Pregnancy Category C: 

There are no adequate and well-controlled studies of SYLATRON in pregnant women. 

Nonpegylated interferon alfa-2b was an abortifacient in Macaca mulatta (rhesus monkeys) at 

15 and 30 million international units (IU)/kg (estimated human equivalent of 5 and 10 million IU/kg, 

based on body surface area adjustment for a 60-kg adult). The estimated INTRON ® A (interferon 

alfa-2b) human equivalent dose of 5 to 10 million IU/kg daily is approximately equal to a human 

equivalent dose of 79 to 158 mcg/kg/week of SYLATRON. Use SYLATRON during pregnancy only 

if the potential benefit justifies the potential risk to the fetus. 

Nursing Mothers 

It is not known whether the components of SYLATRON are excreted in human milk. Studies in 

mice have shown that mouse interferons are excreted in breast milk. Because of the potential 

for adverse reactions from the drug in nursing infants, a decision must be made whether to 

discontinue nursing or discontinue the SYLATRON treatment, taking into account the importance of 

the therapy to the mother. 

Pediatric Use 

Safety and effectiveness in patients below the age of 18 years have not been established. 

Geriatric Use 

Clinical studies of SYLATRON did not include sufficient numbers of subjects aged 65 and over 

to determine whether they respond differently from younger subjects. 

Hepatic Impairment 

SYLATRON has not been studied in patients with melanoma who have hepatic impairment. 

In patients treated for viral hepatitis, peginterferon alfa-2b treatment is contraindicated in those 

with moderate or severe hepatic impairment (Child-Pugh scores >6). Discontinue SYLATRON if 

hepatic decompensation (Child-Pugh scores >6) occurs during treatment. [See Contraindications 

and Warnings and Precautions.] 

Renal Impairment 

The mean area under the concentration-time curve (AUC last 

) following a single dose of 

peginterferon alfa-2b at 1 mcg/kg increased by 1.3-, 1.7- and 1.9-fold in subjects with mild 

(creatinine clearance 50–79 mL/min), moderate (creatinine clearance 30–50 mL/min), and severe 

(creatinine clearance 10–29 mL/min) renal impairment, respectively. After multiple doses, the 

mean AUC tau 

increased by 1.3-fold in moderate and 2.1-fold in severe renal impairment. No 

clinically meaningful amounts of peginterferon alfa-2b were removed during hemodialysis. 

Dose reductions of 25% and 50% are recommended in patients with moderate and severe renal 

impairment, respectively, receiving alpha interferons for chronic hepatitis C. 

The effect of varying degrees of renal impairment on the pharmacokinetics of peginterferon 

alfa-2b at the recommended doses of 3 mcg/kg or 6 mcg/kg for patients with melanoma has not 

been studied. 

OVERDOSAGE 

The experience with overdose of SYLATRON is limited. Patients who were over dosed 

experienced the following adverse reactions: severe fatigue, headache, myalgia, neutropenia, and 

thrombocytopenia. The highest single dose administered was 14 mcg/kg. 

For more detailed information, please read the Prescribing Information. 

LRN#054031-SYL-PWi-USPI.14 

Copyright © 2012 Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc. 

All rights reserved. ONCO-1064624-0000 12/12 

MORE PATIENTS. MORE PRESCRIPTIONS. 

A MORE COMPlETE CONTINuuM Of CARE 

wIThIN yOuR PRACTICE. 

The SpecialTy OncOlOgy neTwOrk frOm iOn SOluTiOnS. 

establishing your own in-practice dispensing service through iOn Solutions 

not only allows your patients more convenient access to medication, but 

it also enhances your control and oversight of their therapy. The Specialty 

Oncology network (SOn) exists to help community oncology practices 

successfully optimize in-practice dispensing services — in fact, 90% of 

all dispensing oncology practices are part of SOn. with the largest and 

longest-tenured pharmacy program in the market, and eight gpO contracts 

currently in place, iOn Solutions harnesses the collective power of community 

oncology to accelerate practice growth and improve patient care. 

For additional information, please visit iononline.com or email 

SON@iononline.com.



LyMPHOMA Review: 

SELECTED HIGHLIGHTS 

FROM ASH 2012 

By: Michael E. Williams, MD, ScM 

Several interesting updates on investigational lymphoma treatment approaches were presented at the Annual 

Meeting of the American Society for Hematology (ASH) this past winter. 

First, it is worthwhile to begin with some data from the 2012 annual meeting of the American Society of Clinical 

Oncology (ASCO). In a Plenary Session at ASCO 2012, Rummel et al. presented data from the prospective, 

multicenter, randomized, Phase III StiL NHL1-2003 trial, which compared the combination of bendamustine 

(Treanda ® )-rituximab (Rituxan ® ) to R-CHOP (rituximab with cyclophosphamide [Cytoxan ® ], doxorubicin, 

vincristine, prednisone) in the first-line treatment of indolent lymphomas and mantle cell lymphoma (MCL) [1]. 

In this study of 549 patients, bendamustine-rituximab significantly improved progression-free survival (PFS) 

and was better tolerated than R-CHOP. The median PFS with this regimen was 69.5 months compared to 

A subset analySIS of this trial, 

31.2 months with R-CHOP. In addition, the benefit of bendamustine-rituximab was observed in all histologic 

PRESENTED at ASH [2], shows 

subtypes except marginal zone lymphoma (MZL), including in both low-risk and high risk follicular lymphoma 

THAT patients who achievED 

(FL). No differences in the rates of secondary malignancies have been observed to date. 

a complete response (CR) 

FOLLOWING first-LINE treatment 

HAD a significantly longer 


A subset analysis of this trial, presented at ASH [2], 

shows that patients who achieved a complete response 

(CR) following first-line treatment had a significantly longer 

PFS and overall survival (OS) compared to those who 

achieved only a partial response (PR), suggesting an 

association between quality of response and outcome. 

Overall, the results of StiL NHL1 establish bendamustinerituximab 

as a front-line regimen for indolent B cell non- 

Hodgkin lymphoma (NHL) and non-transplant-eligible 

MCL. More data on OS and potential long-term toxicities, 

including risk of myelodysplastic syndromes (MDS) and 

second primary cancers, are needed before determining 

whether B-R should be the preferred initial treatment. 

Detailed results from StiL NHL1 have been recently 

published on-line in Lancet Oncology. 

Final results from the MCL Younger Trial, conducted by 

the European Mantle Cell Lymphoma Network, were 

presented at this winter’s meeting by Hermine et al. [3]. 

This randomized trial compared the following treatments 

in previously untreated MCL patients (N=497; stage II-IV) 

PFS and ovERALL survivAL 

(OS) compared to those 

WHO achievED only a partial 

RESPONSE (PR), suggesting an 

ASSOCIATION between quality of 

RESPONSE and outcome. 

oncologistics 31



age 65 and younger: 

> 6 courses of R-CHOP followed by myeloablative 

radiochemotherapy and autologous stem cell 

transplant (ASCT) 

> Alternating courses of 3x R-CHOP and 3x R-DHAP 

(rituximab plus dexamethasone, high-dose cytarabine 

> 79.6% by FDG-PET (n=162) after 4 courses of R-DHAP 

(International Harmonization Project [IHP] criteria). 

> 89% by FDG-PET (n=121) after ASCT (IHP criteria). 

Response rates with R-DHAP followed by ASCT (without total 

body irradiation in the conditioning regimen) also compared 

Table 1: Phase II Study of Lenalidomide Plus Rituximab in Untreated, Advanced-Stage Indolent Non-Hodgkin 

Lymphoma: Response Rates 

Response 

Histology 

Follicular Lymphoma 

Marginal Zone 

Lymphoma 

Small Lymphocytic 

Lymphoma 

All Evaluable 

Patients 

[AraC, Cytosar-U ® ], and cisplatin [Platinol®]) followed 

by a high-dose cytarabine-containing myeloablative 

favorably with other chemotherapy regimens. However, the 

impact of this regimen in terms of event-free survival (EFS), 

(n=46) 

(n=27) 

(n=30) 

(N=103) 

radiochemotherapy regimen and ASCT 

The primary endpoint was time to treatment failure (TTF). 

PFS, and OS still needs to be investigated, as well as the 

role of transplant versus other consolidation strategies and 

maintenance therapy 

ORR 98% 89% 80% 90% 

CR/CRu 87% 67% 27% 64% 

PR 11% 22% 53% 25% 

ASCT was performed and documented at a similar rate 

in both arms (R-CHOP: 83% vs. R-DHAP: 80%), with a 

response rate of 98% in both arms after ASCT. In addition, 

Taken together, the results of the MCL Younger Trial and 

LyMa show that high-dose cytarabine and ASCT are 

important components of treatment in younger MCL patients. 

SD 2% 11% 13% 7% 

PD 0 0 7% 2% 

both induction arms achieved a similar rate of complete 

–– 

Abbreviations: ORR=objective response rate; CR=complete response; CRu=complete response, unconfirmed; 

response (CR; R-CHOP: 62% vs. R-DHAP: 61%). With 

Several studies at ASH focused on the use of lenalidomide 

PR=partial response; PD=progressive disease (Source: Fowler et al. Proc ASH 2012; Abstract 901). 

a median follow up of 53 months, TTF was significantly 

(Revlimid ® ) in the treatment of lymphoma, further 

better with alternating courses of R-CHOP/R-DHAP than 

demonstrating that it is an active agent in follicular lymphoma 

with R-CHOP (88 months vs. 46 months, respectively; 

(FL) and MCL. 

p=0.0382, Hazard Ratio [HR]: 0.68), with benefits observed 

across all prognostic groups. The R-DHAP regimen was 

First, Fowler et al. presented the final results of a Phase II 


also associated with improvement in overall survival (OS; 

not reached [NR] vs. NR, respectively; p=0.0485) and with 

achievement of minimal residual disease (MRD) negativity, a 

predictor of PFS. It also exhibited an acceptable safety profile. 

These final results demonstrate that alternating courses 

of R-CHOP/R-DHAP followed by a high dose cytarabinecontaining 

myeloablative regimen and ASCT significantly 

improves TTF, and that induction regimens containing high 

dose cytarabine followed by ASCT should become a new 

standard of care in younger MCL patients. 

The randomized, open-label, phase III LyMA study was 

conducted to evaluate the efficacy of rituximab maintenance 

therapy in younger MCL patients (ages 18-66 years) 

undergoing first-line treatment with 4 courses of R-DHAP 

and exhibiting a response after ASCT. An analysis of clinical, 

metabolic and molecular response data from this trial shows 

that R-DHAP induction alone prior to ASCT provides a high 

CR and CR unconfirmed (CR/CRu) rate, as demonstrated 

by both FDG-PET and assessment of MRD [4]. The CR/CRu 

rates by assessment criteria were: 

> 76.5% in the intent-to-treat population (n=199) after 4 

courses of R-DHAP (Cheson 99 criteria). 

study investigating lenalidomide plus rituximab for untreated, 

advanced-stage indolent non-Hodgkin lymphoma (NHL) [5]. 

Patient histologies included FL, marginal zone lymphoma 

(MZL), and small lymphocytic lymphoma (SLL). 

Front-line lenalidomide and rituximab produced high 

overall and complete response rates (Table 1) with durable 

remissions in the majority of patients and a projected 3-year 

PFS of 81% in FL, 89% in MZL, and 66% in SLL. 

The toxicity profile of lenalidomide-rituximab was mild, with 

manageable hematologic side effects. Grade 3/4 neutropenia 

occurred in 41% of patients and thrombocytopenia 

occurred in 6% of patients. Five patients developed grade 

3 neutropenic fever. The most common grade 3/4 nonhematologic 

toxicities included muscle pain (8%), rash (7%), 

and fatigue (5%). Five secondary malignancies were reported. 

Phase III randomized trials investigating this combination in 

untreated FL are underway. 

The Phase II, multicenter, single-arm, open-label MCL-001 

EMERGE study investigated single-agent lenalidomide (25 

mg/d PO on days 1-21 of a 28-day cycle) in MCL patients 

who had relapsed on, progressed after, or were refractory 

to bortezomib (Velcade®) [6]. The primary endpoints were 

overall response rate (ORR) and duration of response. 

Lenalidomide demonstrated rapid and durable efficacy 

in MCL patients who had failed prior therapies, including 

bortezomib. In this heavily pretreated patient population 

(N=134; median prior therapies: 4), the ORR to singleagent 

lenalidomide was 28%, with a CR/CRu rate of 8% by 

independent central review. The median duration of response 

was 16.6 months and the median time to response was 2.2 

months. The median PFS was 4.0 months, while median OS 

was 19.0 months. 

The most frequent adverse event (≥ 5% grade 3/4) was 

myelosuppression, consistent with the known safety profile 

for lenalidomide in NHL. 

Based on these and other promising data, lenalidomide will 

likely become a standard approach for relapsed disease and 

for maintenance or consolidation therapy in MCL. 

Emerging data suggests that the addition of lenalidomide 

to R-CHOP is feasible and effective. In a Phase II study 

presented by Nowakowski et al., the combination of 

lenalidomide (25 mg day 1-10 of a 28 day cycle) with R-CHOP 

(R2CHOP) was shown to be well tolerated and effective as 

initial therapy for aggressive B-cell lymphomas [7]. In adults 

with newly diagnosed CD20 positive diffuse large B cell 

(DLBCL) or grade 3 FL (n=47), the ORR was 98%, CR was 

83%, and PR was 15%, and the addition of lenalidomide to 

R-CHOP also appeared to ameliorate the negative effect of 

the non-germinal center B-cell phenotype on outcome. The 

efficacy of this regimen also appears to be promising when 

compared to an R-CHOP treated historical cohort, with a 

12-month PFS of 73% for R2CHOP versus 62% for the casematched 

R-CHOP controls. 

R2CHOP was well tolerated, including in elderly patients. 

Grade 3/4 adverse events were mainly hematological. 

Although grade 4 neutropenia was common (70%), infectious 

complications were rare. Grade 4 thrombocytopenia 

occurred in 20% of patients without bleeding complications, 

and thrombosis occurred in 1 patient (1%), similar to the 

oncologistics 33



risk reported for NHL patients. One death was reported 

(perforation/sepsis). 

Randomized trials are in progress to further evaluate 

R2CHOP in comparison to R-CHOP. 

Another interesting agent being investigated for lymphoma 

treatment is the orally administered Bruton’s tyrosine kinase 

(BTK) inhibitor, ibrutinib (PCI-32765), with several studies 

showing that the BCR pathway is highly targetable in B-cell 

malignancies. In a report by Fowler et al., long-term followup 

from a Phase I study of ibrutinib shows it to be active 

and well tolerated in relapsed FL [8]. In 9 patients who 

received a dose of 5 mg/kg/day or more, 3 CRs and 2 PRs 

were reported. The median duration of response among 

this group was 12.3 months and the median PFS was 19.6 

months. There was no cumulative toxicity with extended 

dosing, and response improved with continued treatment 

in some patients. Based on drug occupancy and clinical 

responses, a dose of 560 mg daily is recommended for 

future FL studies. Phase II studies in FL are currently being 

planned. 

In relapsed/refractory MCL, interim results from a Phase 

II study continue to show that ibrutinib (560mg daily in 

continuous 28-day cycles) is highly active in this population 

[9]. In the efficacy- evaluable participants (n=51), the 

ORR was 69% for all patients and was similar among 

both bortezomib-naïve (n=31) and bortezomib-exposed 

patients (n=20) (71% vs. 65%, respectively). Few grade 3/4 

hematologic adverse events were observed (n=61) included 

neutropenia (5%), febrile neutropenia (3%), anemia (3%), 

thrombocytopenia (3%), and pancytopenia (2%). 

Brentuximab vedotin (Adcetris ® ) is an anti-CD30 

monoclonal antibody conjugated by a protease-cleavable 

linker to a microtubule-disrupting agent, monomethyl 

auristatin E (MMAE). In an open-label, multicenter Phase I 

study in Hodgkin lymphoma, this agent was administered 

with standard ABVD therapy (doxorubicin [Adrimycin ® ], 

bleomycin [Blenoxane ® ], vinblastine [Velban ® ], and 

dacarbazine [DTIC-Dome ® ]) or a modified standard 

(AVD; adriamycin, vinblastine, and dacarbazine) [10]. 

This study showed that brentuximab can be combined 

with AVD chemotherapy, but cannot be given 

concomitantly with bleomycin due to pulmonary toxicity. 

Aside from this, AVD combined with brentuximab 

appeared to be well tolerated with manageable adverse 

effects and a CR rate of 86% at the end of frontline 

therapy. The recommended regimen is 1.2 mg/ 

kg brentuximab every 2 weeks combined with AVD. 

A multinational Phase III study is ongoing to assess 

brentuximab in combination with AVD compared to ABVD 

alone in treatment-naïve Hodgkin lymphoma patients. 

References 

1. Rummel MJ, Niederle N, Maschmeyer G, et al. 

Bendamustine plus rituximab (B-R) versus CHOP plus 

rituximab (CHOP-R) as first-line treatment in patients with 

indolent and mantle cell lymphomas (MCL): Updated results 

from the StiL NHL1 study. J Clin Oncol 30, 2012 (suppl; 

abstr 3). 

2. Rummel MJ, Niederle N, Maschmeyer G, et al. Subanalysis 

of the StiL NHL 1-2003 Study: Achievement of Complete 

Response with Bendamustine-Rituximab (B-R) and 

CHOP-R in the First-Line Treatment of Indolent and Mantle 

Cell Lymphomas Results in Superior Survival Compared to 

Partial Response. Proc ASH 2012; Abstract 2724. 

3. Hermine O, Hoster E, Walewski J, et al. Alternating Courses 

of 3x CHOP and 3x DHAP Plus Rituximab Followed by 

a High Dose ARA-C Containing Myeloablative Regimen 

and Autologous Stem Cell Transplantation (ASCT) 

Increases Overall Survival When Compared to 6 Courses 

of CHOP Plus Rituximab Followed by Myeloablative 

Radiochemotherapy and ASCT in Mantle Cell Lymphoma: 

Final Analysis of the MCL Younger Trial of the European 

Mantle Cell Lymphoma Network (MCL net). Proc ASH 2012; 

Abstract 151. 

4. Le Gouill S, Callanan M, Macintyre E, et al. Clinical, 

Metabolic and Molecular Responses After 4 Courses of 

R-DHAP and After Autologous Stem Cell Transplantation for 

Untreated Mantle Cell Lymphoma Patients Included in the 

LyMa Trial, a Lysa Study. Proc ASH 2012; Abstract 152. 

5. Fowler NH, Neelapu SS, Hagemeister FB, et al. 

Lenalidomide and Rituximab for Untreated Indolent 

Lymphoma: Final Results of a Phase II Study. Proc ASH 

2012; Abstract 901. 

6. Goy A, Sinha R, Williams ME, et al. Phase II Multicenter 

Study of Single-Agent Lenalidomide in Subjects with Mantle 

Cell Lymphoma Who Relapsed or Progressed After or Were 

Refractory to Bortezomib: The MCL-001 “EMERGE” Study. 

Proc ASH 2012; Abstract 905. 

7. Nowakowski GS, LaPlant BR, Craig Reeder C, et al. 

Combination of Lenalidomide with R-CHOP (R2CHOP) Is 

Well-Tolerated and Effective As Initial Therapy for Aggressive 

B-Cell Lymphomas - A Phase II Study. Proc ASH 2012; 

Abstract 689. 

8. Fowler NH, Advani RH, Sharman JP, et al. The Bruton’s 

Tyrosine Kinase Inhibitor Ibrutinib (PCI-32765) Is Active and 

Tolerated in Relapsed Follicular Lymphoma. Proc ASH 2012; 

Abstract 156. 

9. Wang M, Rule SA, Martin P, et al. Interim Results of an 

International, Multicenter, Phase 2 Study of Bruton’s 

Tyrosine Kinase (BTK) Inhibitor, Ibrutinib (PCI-32765), in 

Relapsed or Refractory Mantle Cell Lymphoma (MCL): 

Durable Efficacy and Tolerability with Longer Follow-up. 

Proc ASH 2012; Abstract 904. 

10. Ansell SM, Connors JM, Park SI, O’Meara MM, Younes A. 

Frontline Therapy with Brentuximab Vedotin Combined with 

ABVD or AVD in Patients with Newly Diagnosed Advanced 

Stage Hodgkin Lymphoma. Proc ASH 2012; Abstract 798. 


Michael E. Williams, MD, ScM is byrd s. leavell 

professor of medicine chief, Hematologic Malignancies 

Section Hematology/Oncology Division, University of 

Virginia Cancer Center, Charlottesville, VA 

Disclosure: Grant support - Celgene, Cephalon, 

Genentech, Millennium; Pharmacyclics Consultant - 

Celgene, Genentech, Millennium, Pharmacyclics 

oncologistics 35

eimbursement watch 

oncologistics reimbursement watch 

GETTING READy FOR 

Health INSURANCE 

EXCHANGES 

By: Zachary Bridges 

Beginning in January of 2014, U.S. residents and small businesses will be able to purchase insurance 

coverage through newly created health insurance exchanges. Whether obtaining coverage for the first time or 

transitioning from an employer-sponsored insurance plan, patients purchasing coverage through one of the 

Qualified Health Plans (QHPs) sold through the exchanges will have a new benefit structure. A major concern 

expressed by the cancer community has been whether QHPs will provide access to the most appropriate 

oral and physician-administered therapies for individual patients. 


Physicians rely on the drug margin revenue to cover 

It will be months before exchange plans publish 

their coverage criteria, formularies, and cost-sharing 

requirements. However, recent regulatory guidance gives 

some insights into how this coverage picture will look. 

Tracking these developments will give your practice an 

advantage in terms of helping your patients to select 

exchange plans that will enable them to continue on 

needed therapies and avoid obstacles that could impede 

access to care. 

BACKGROUND ON EXCHAnges 

Mandated by the Patient Protection & Affordable Care Act 

(ACA), health insurance exchanges are intended to be a 

marketplace where patients without access to affordable 

employer-sponsored health plans can purchase health 

insurance. The ACA requires that all QHPs offered 

through exchanges provide patients with a minimum level 

of coverage known as “essential health benefits” (EHBs). 

The EHB package includes coverage for 10 benefit 

categories such as prescription drugs. 

The required categories of essential health benefits (EHBs) 

for any plans sold through health insurance exchanges 

include the following: 1) ambulatory patient services 

(2) emergency services (3) hospitalization (4) maternity 

and newborn care (5) mental health and substance use 

disorder services including behavioral health treatment 

(6) prescription drugs (7) rehabilitative and habilitative 

services and devices (8) laboratory services (9) preventive 

and wellness services and chronic disease management 

and (10) pediatric services, including oral and vision care. 

THE required categories of essential health benefits 

(EHBs) for any plans sold through health insurance 

EXCHANGES include the following: 1) ambulatory patient 

SERvICES (2) emergency servICES (3) hospitalization (4) 

MATERNITy and newborn care (5) mental health and 

SUBSTANCE use disorder servICES including behavIORAL 

HEALTH treatment (6) prescription drugs (7) rehabilitative 

AND habilitative servICES and devICES (8) laboratory 

SERvICES (9) prevENTIve and wellness servICES and chronic 

DISEASE management and (10) pediatric servICES, including 

ORAL and vISION care. 

oncologistics 37

eimbursement watch 

oncologistics reimbursement watch 

In recent months, states had to select “benchmark plans” 

that will act as models for other QHPs operating in 

that state. The benchmarks were selected from the 

following options: 

> Largest plan by enrollment in any of the 3 largest 

small-group insurance products in a given state’s 

small-group market 

> Any of the 3 largest state employee health benefit 

plans by enrollment 

> Any of the 3 largest national Federal Employees 

Health Benefits Program (FEHBP) plan options 

> Largest insured commercial non-Medicaid HMO 

operating in a state 

class listed in the U.S. Pharmacopeia Medicare 

Model Guidelines for formularies, or 

> The same number of drugs in each category and 

class as the state’s benchmark plan 

That means there is some potential that an exchange 

plan may only have to cover a single therapy in a given 

drug class with no special exceptions for oncology 

or hematology. This is a significant change from the 

requirements for plans offering coverage to Medicare Part 

D beneficiaries: Part D plans are required to offer open 

access to products in 6 protected therapeutic classes, 

which include anti-cancer treatments. 


For any states that did not select a benchmark, the U.S. 

Department of Health & Human Services (HHS) used the 

first criterium listed above as the default for selecting a 

plan. A full listing of the benchmark plans can be found 

at the Center for Consumer Information and Insurance 

website at http://cciio.cms.gov/. 

Open enrollment in the exchanges starts October 1, 

2013. Oncology and hematology practices may want to 

consider reviewing the formularies for the benchmark 

plan in their respective states now to gain insights into the 

coverage parameters for key therapies. 

ehb Final Rule 

In February 2013, HHS released additional regulations 

about the EHB package of benefits that will be offered 

in all QHPs. According to the EHB final rule, access in 

exchange plans can be defined in a couple ways, such as 

formulary offerings and patient cost sharing. The final rule 

established broad parameters to ensure QHPs provide 

access to clinically necessary treatments and outlined 

limitations on beneficiaries’ maximum deductibles and 

yearly out-of-pocket costs. 

Prescription Drug Coverage 

According to the final rule, exchange plans must cover the 

greater of: 

> One drug in every therapeutic category and 

However, similar to Part D, exchange plans will be 

required to implement procedures such as appeals or 

exceptions processes that will facilitate patient access to 

drugs that are not on a formulary. Additional regulatory 

guidance on this subject is pending. In the case of 

Medicare Part D plans, this often means that a physician 

must submit a letter explaining the clinical need for the 

patient to be on a specific, non-covered medication. 

Currently, many private insurance plans offer favorable 

access to anti-cancer drugs. That could bode well for 

coverage of oncology therapies under exchange plans, 

since one of the benchmark plan options for states 

was to select a popular plan sold in that state with a 

high enrollment. 

Cost-Sharing Requirements 

The limitations on patient cost sharing outlined in the final 

rule establish general parameters for annual deductibles 

and maximum out-of-pocket limits. However, the final rule 

did not address limits for patient out-of-pocket spending 

on prescription drugs. Beginning in January 2014, the 

maximum deductible an exchange plan can require is 

$2,000 for an individual or $4,000 for a family. Limits on 

annual out-of-pocket spending are $6,250 for individuals 

or $12,500 for families. However, cost-sharing and annual 

deductible limits for network benefit plans apply only 

for services furnished by participating providers. Costsharing 

for benefits furnished by out-of-network providers 

will not count towards these annual limitations. Thus, 

patients who obtain care from out-of-network providers could 

see higher costs. 

In not addressing the issue of prescription drug costs, 

HHS allowed states the flexibility to establish cost-sharing 

limitations within their exchanges. While the EHB final rules 

did not provide much insight on this topic, some states such 

as California have begun to release-more detailed regulations 

for participating QHPs. The regulations released provide 

specific benefit design details for plans that are purchased 

through the exchange named Covered California, and include 

cost-sharing information including, annual deductibles, office 

visit copayments, and prescription copayments for brand and 

generic drugs. 

What This Means for Your PrACtice 

and Patients 

HHS has left states with a certain level of flexibility to 

encourage new and innovative plan benefit designs. 

Considering that cost containment is a significant focus for 

the health insurance industry as a whole, it is reasonable 

to assume that plan structure and benefit designs 

available within the exchanges will follow suit. Utilizationmanagement 

strategies such as prior authorization, step 

therapy requirements, and tiered formularies will continue 

to be employed as a tool for managing high-cost specialty 

medications. It will be important for oncology and hematology 

practices to have an understanding of which oral and 

physician-administered therapies are covered under the major 

exchange plans in their region and also be familiar with any 

“state-required benefits.” One additional provision of the EHB 

final rule was that “state-required benefits” enacted on or 

before December 31, 2011, must be included in all QHPs. As 

2014 approaches, states may release more-clearly defined 

regulations for QHPs. Practices should monitor and review 

any and all state regulations for how they might impact their 

patients’ access to care. 

One of the primary goals of the ACA was to provide coverage 

options for the 55 million Americans who are currently 

uninsured. It is notable that of the 24 million Americans 

expected to enroll in exchange plans by 2016, 20 million are 

expected to qualify for income-based federal assistance 

that, depending on the recipients’ income levels, could range 

from tax subsidies to help with premiums; to cost-sharing 

assistance with deductibles, co-payments, or co-insurance; 

to additional limits on out-of-pocket spending. 1 However, even 

though assistance will be available for many if their incomes 

fall between 100% and 400% of the federal poverty level 

(FPL)* many exchange plan enrollees are still likely going to 

oncologistics 39


reimbursement watch 

face challenges affording insurance and their share of the exchange plan enrollees, like their Medicare counterparts, 

costs of therapy. 2 

will have to seek cost-sharing support from independent, 

charitable copayment assistance foundations. 

*2013 Federal Poverty Guidelines 3 

Persons In Household Poverty Guideline 

1 $11,490 

2 $15,510 

3 $19,530 

4 $23,550 

5 $27,570 

6 $31,590 

7 $35,610 

8 $39,630 

1 

Congressional Budget Office’s February 2013 Estimate of the 

Effects of the Affordable Care Act on Health Insurance Coverage 

2 

Patient Protection and Affordable Care Act, Pub. L. No. 111- 

148, §1401, 124 Stat. 215 (2010). 

3 

78 Fed. Reg. 5183 (Jan 24, 2013) available at http://www.gpo. 

gov/fdsys/pkg/FR-2013-01-24/pdf/2013-01422.pdf. 

Just as they do now, underinsured patients will need 

access to sources of financial support so that healthcare 

costs do not adversely impact their compliance with 

therapy. It will be important for practices to keep abreast 

of new regulatory developments from bodies like the 

Office of the Inspector General (OIG), assistance program 

policies among manufacturers, and communications from 

charitable copayment foundations. For example, while 

many privately insured patients with high deductibles and 

copayments currently receive cost-sharing assistance 

TIPS FOR PRACTICES 

> Monitor new information from HHS, OIG, and your 

state regarding exchange plans, required benefits, 

cost-sharing, and patient eligibility for manufacturer 

assistance programs 

> Plan to contact charitable copay foundations, 

manufacturer copay card programs, and 

manufacturer patient assistance (free drug) programs 

toward the end of 2013 to verify whether they are 

planning any changes to their program policies and, 

in particular, how they plan to support patients who 

enroll in exchange plans 

> Review information from your specialty societies, 

group purchasing organizations, and patient 

advocacy groups to keep abreast of critical 

information related to healthcare reform 

implementation 

> Review details about your state’s exchange 

benchmark plan now to get a better sense of how 

other exchange plans that will be available in your 

state will cover key therapies 

Once your state selects the qualified health plans that 

will be sold in the exchanges, become familiar with those 

plans’ formularies, coverage policies, and cost-sharing 

requirements so you can be an effective source of 

information for your patients who are considering enrolling 

in an exchange plan. 

from branded copay cards offered by manufacturers, 

there has been no regulatory guidance issued on the 

subject of whether exchange plan enrollees will be eligible 

for such programs. In the absence of regulation, it means 

that manufacturers who offer brand copay assistance to 

exchange plan enrollees risk the possibility of violating 

federal anti-kickback rules. It is possible that underinsured 

Zachary Bridges is manager, Xcenda Reimbursement 

Strategy & Trends. 

CONGRESS: 

Fight Cancer. 

NOT Cancer Care. 

Thanks to advances in cancer care in America, lives are being 

saved everyday. But unfortunately, our nation is facing a crisis 

in cancer care that could negatively impact patient access, quality 

and availability of critical medications and therapies. 

Financial pressures resulting from repeated cuts to Medicare 

reimbursement for life-saving therapies are forcing some cancer 

centers to shut their doors. 

These closures have led to patient access challenges, 

clinical staff reductions and higher Medicare 

costs because of cancer patients seeking 

care in more expensive settings. 

Sequestration and some deficit reduction 

proposals further threaten America’s 

community cancer centers, cancer 

doctors and their vulnerable patients. 

Any more cuts to community cancer 

care must be stopped. 

While America’s 

cancer patients 

fight for their 

lives, let’s fight 

to protect their 

community 

cancer care. 

To learn more, visit www.communityoncology.org

Hematology - ION Solutions

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