Annual Meeting Proceedings Part 1 - American Society of Clinical ...

66s Breast Cancer—Triple-Negative/Cytotoxics/Local Therapy
1068 General Poster Session (Board #23C), Sat, 8:00 AM-12:00 PM
Patient-reported pain and other symptoms as prognostic factors for overall
survival (OS) in a phase III clinical trial of patients with advanced breast
cancer. Presenting Author: Wei Shen, Eli Lilly and Company, Indianapolis,
IN
Background: The safety and efficacy of gemcitabine plus paclitaxel versus
paclitaxel in advanced breast cancer after anthracycline-based adjuvant
therapy has been reported previously (Albain et al. 2008). This post-hoc
analysis evaluates the prognostic effect of baseline scores of the Brief Pain
Inventory short form (BPI-SF) and the Rotterdam Symptom Checklist
(RSCL) on OS. Methods: Patients completed theBPI-SF and the RSCL. BPI
“worst pain” item and BPI interference subscale scores range from 0 (no
pain or interference with daily living) to 10. Four RSCL subscales were
transformed to 0-100, with 100 as best score. Univariate Cox models were
used to determine the prognostic effect of each measure on OS. Multivariate
Cox models were used to determine the prognostic effect of each
measure in the presence of 11 demographic/clinical variables, including
Karnofsky performance status, age, and estrogen and progesterone receptor
status. Kaplan-Meier curves and log-rank tests were used to compare OS
among patient groups categorized using clinically meaningful thresholds
and the sample median of the BPI and RSCL scores. Results: Randomized
patients were evaluable for this analysis (n�529). In the univariate
analysis, significant prognostic effects on OS were observed for baseline
scores of both BPI measures (worst pain and interference) (HRs, 1.07 for
1-point increase; all p�0.0042) and three out of four RSCL subscales
(activity level, physical distress, quality of life) (HRs, 0.86-0.91 for
10-point increase; all p�0.0120). In the multivariate Cox models, BPI
worst pain remained as a significant prognostic factor (p�0.0245), as did
RSCL activity level (p�0.0004). The median OS for patients with BPI worst
pain score 0 (no pain) was 23.8 months (mos) versus 17.9 mos and 14.8
mos for scores 1-4 (mild) and 5-10 (moderate/severe) (log-rank p�0.0066).
The median OS was 23.8 mos for patients with RSCL activity scores greater
than or equal to the sample median (�95.2) versus 14.6 mos for patients
with scores �95.2 (log-rank p�0.0001). Conclusions: This retrospective
analysis resulted in strong evidence that BPI-SF and RSCL provide distinct
prognostic information for OS.
1070 General Poster Session (Board #23E), Sat, 8:00 AM-12:00 PM
Phase I trial of ixabepilone and vorinostat in metastatic breast cancer.
Presenting Author: Thehang H. Luu, City of Hope, Duarte, CA
Background: VOR, an HDAC inhibitor, induces acetylation of tubulin, and
decreases resistance by attenuating downstream activation of AKT, c-Raf
and HER-2. Patients (pts) with MBC treated with VOR had a TTP of 8.5
months (range 4-14) and stable disease in 29% (Luu et al., 2008). Our
preclinical data showed synergistic effect of IXA and VOR in MDA-MB-231
and MCF7. Methods: The primary aims were to: 1) define the maximum
tolerated dose (MTD) based on dose limiting toxicities (DLT), and 2)
describe the pharmacokinetics (PK) of 2 schedules of VOR and IXA.
Secondary aims were to describe: 1) response rate (RR) and 2) clinical
benefit rate (CBR). The study included: 1) pts with MBC; 2) ECOG PS 0-2;
3) adequate marrow and organ functions; 4) no prior IXA or VOR; and 5) �
grade (gr) 1 neuropathy. Stable brain metastasis were allowed. Pts were
randomized to schedule A: VOR (QDx14) � IXA (D2) Q21D; or B: VOR
(D1-7 and 15-21) � IXA (D2, 9, 16) Q28D. A modified toxicity probability
interval design (target toxicity rate� 0.2 and equivalence range �/- 0.05)
(Ji et al, 2010) determined dose escalation guidelines. PK were assessed
with LC-MS/MS assays. Results: Among 37 pts randomized, 36 were
evaluable [median age (55 yrs); median prior chemotherapy regimens (3);
ER and/or PR � (64%); HER2 � (19%)]. In cohort A, 16 pts were treated
(1 inevaluable). The MTD was: VOR 300mg (QDx14) � IXA (32mg/m2 D2)
Q21D (dose level 1). DLT was experienced by 27% (4/15) pts [gr 4
neutropenia, gr 3 fatigue/AST, hyponatremia and allergic reaction to IXA].
In cohort B, 21 pts were treated (dose level 1, n�15; dose level 2, n�6).
The MTD was VOR 300mg QD (D1-7 and 15-21) � IXA 16mg/m2 (D2, 9,
16) Q28D (dose level 1), no DLTs were observed. Dose level 2 was closed
with 50% (3/6) of pts experiencing DLTs [gr 3 neutropenia, hypertension,
and hypokalemia]. Median cycles treated (cohort A: 6, cohort B: 4).
Response in cohort A and B respectively was: 1 CR, 2 PR, 7 SD (RR: 20%,
CBR: 67%) and 1 CR, 4 PR, 9 SD (RR: 33%, CBR: 93%). VOR and IXA PK
were not influenced by the presence of the other drug, clearance values�
220 L/h and 20 L/h/m2 , respectively. Conclusions: We established the MTD
of VOR and IXA in pts with MBC. The combination demonstrated clinical
activity in these heavily pretreated pts. Further studies are recommended.
1069 General Poster Session (Board #23D), Sat, 8:00 AM-12:00 PM
Cost-effectiveness analysis using a Markov model assessing the addition of
bevacizumab to paclitaxel in HER2-negative metastatic breast cancer
patients. Presenting Author: Tamer Refaat, Northwestern University, Chicago,
IL
Background: Metastatic breast cancer (MBC) remains an incurable disease
despite advances in treatment modalities. In 2008, Eastern Cooperative
Oncology Group 2100 trial (E2100) results led to FDA approval for
bevacizumab with paclitaxel in the initial treatment of HER2-negative
MBC. The addition of bevacizumab to paclitaxel led to a gain of around 2.5
months of progression-free survival (PFS), no significant benefit on overall
survival (OS), and increased toxicity. In November 2011, the FDA officially
revoked approval of bevacizumab for HER2-negative MBC. However, both
the European Medicines Agency (EMEA) and NCCN still endorse bevacizumab
for this indication. One of the greatest challenges facing healthcare
worldwide is reconciling incremental clinical benefits with exponentially
rising costs. This study aimed to assess the cost-effectiveness of bevacizumab
with paclitaxel for HER2-negative MBC. Methods: A Markov decision
tree using Data 3.5 (TreeAge Software, Inc.) was created to do decision and
cost-effectiveness analyses of using bevacizumab in combination with
paclitaxel versus paclitaxel alone as first-line chemotherapy in HER2negative
MBC using efficacy and toxicity data from the E2100 study. Costs
were obtained from the Center for Medicare Services Drug Payment Table
and Physician Fee Schedule. The model was designed from the patient and
payer perspectives and sensitivity analyses were run. Results: The marginal
cost between paclitaxel alone versus bevacizumab and paclitaxel was 86K
with a marginal efficacy of 0.369 quality-adjusted life-years and marginal
cost effectiveness of 232,720.72 USD. The expected outcome value was
1.86 for bevacizumab and paclitaxel and 1.67 for paclitaxel alone.
However, the combination was not cost effective and only a marginal
survival advantage that was not significant was observed. Conclusions: This
study demonstrates that, despite a significant PFS advantage, the addition
of bevacizumab to paclitaxel is not cost-effective for patients with HER2negative
MBC. Such data could be informative to policymakers who
consider the health economics and incremental cost-effectiveness of
medical therapies.
1071 General Poster Session (Board #23F), Sat, 8:00 AM-12:00 PM
Outcomes of 47 patients with human immunodeficiency virus infection
treated for breast cancer: A 20-year experience. Presenting Author: Roberto
Enrique Ochoa, University of Miami, Miami, FL
Background: Patients (pts) with Human Immunodeficiency Virus (HIV) are
living longer and non-AIDS defining malignancies have been increasingly
reported in these patients. Methods: Retrospective review identified 47 pts
with breast cancer (BC) and HIV who were seen at the University of Miami
Sylvester Comprehensive Cancer Center/Jackson Memorial Hospital between
January 1999 and June 2011. Results: Pt characteristics: 46
female, 1 male, mean age 46 years (range 31-65). Race: African American
79%, Caucasian 21%. Ethnic: Hispanics 14%, non-Hispanics 86%.
Premenopausal 68% postmenopausal 32%. Tumor characteristics: Stage:
Tis 4%, Stage I: 6%,Stage II: 38%, Stage III: 38%, Stage IV: 9%. ER
positive (50%) her-2 positive (15%), Triple negative (21%). HIV characteristics:
36 pts with HIV before or concurrent with the diagnosis of BC. 6 pts
diagnosed with HIV within 1 year of BC diagnosis. HIV dx date unavailable
in 5 pts. 27% had AIDS. CD4 counts (in cells/�L)were: � 500 (23%);
201-500 (37%), 51 – 200 (20%) � 50 (20%). 15 pts were diagnosed with
BC in preHAART era. Of those dx with BC after 1996, 60% were on HAART.
BC treatment: 43 pts had localized disease. 32 underwent modified radical
mastectomy, 8 breast conservation and 3 pts refused surgery. 26 pts
received curative or palliative chemotherapy. Complications of BC treatment:
serious side effects were reported in 11 (42%) including neutropenic
fever/sepsis (10 pts), ARDS (1 pt). Zoster infection was reported in 12% of
the pts. 3 patients developed rapidly progressive and fatal AIDS within 6
months of completion of chemotherapy. Survival: See Table. Conclusions:
BC in patients with HIV infection spans the spectrum of BC presentations.
Hormonal therapy, surgery and radiation therapy were well tolerated.
Infectious complications were common in patients treated with chemotherapy
and routine use of growth factors and prophylactic acyclovir should
be considered.
Alive (% pts) Died BC (% deaths) Died HIV (% deaths)
Tis 3 1 (50) 1 (50)
Stage I 3 (100) 0 0
Stage II 8 (50) 3 (38) 4 (50)
Stage III 3 (28) 4 (67) 2 (33)
Stage IV 0 4 (100) 0
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