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

1080 General Poster Session (Board #24G), Sat, 8:00 AM-12:00 PM
Baseline comprehensive geriatric assessment to predict for toxicity of
single-agent chemotherapy in elderly metastatic breast cancer patients:
Results from the OMEGA study of the Dutch Breast Cancer Trialists’ Group.
Presenting Author: Marije Hamaker, Diakonessenhuis, Utrecht, Netherlands
Background: A comprehensive geriatric assessment (CGA) systematically
appraises the somatic, psychosocial and functional health status of elderly
patients. If CGA can predict toxicity of chemotherapy in elderly cancer
patients, this assessment could be useful in deciding on optimal treatment.
In this analysis, we evaluated the association between frailty on CGA or
Groningen Frailty Index (GFI), and grade 3/4 toxicity in metastatic breast
cancer (MBC) patients treated with first-line chemotherapy. Methods: In the
OMEGA study, MBC patients (� 65 years) were randomized between
PEGdoxo 45mg/m2every 4 weeks or capecitabine 2000 mg/m2 on days
1-14 every 3 weeks. Baseline geriatric assessment included functional
status (ECOG performance status (PS), IADL), cognition (MMSE), mood
(GDS), comorbidity (Charlson), polypharmacy and undernutrition (BMI)
and GFI. Frailty on CGA was defined as one or more of the following:
IADL�13, MMSE �23, GDS �5, BMI �20, �5 medications or Charlson
�2. GFI score for frailty was �4. Results: In total, 78 patients were
randomized (PEGdoxo 38, capecitabine 40), median age 75 years (range
65-86). ECOG PS was 0-1 in 78% of patients and 2-3 in 22%. So far, 72
patients were evaluable for toxicity and baseline CGA. Overall, 50 patients
(70%) were frail on CGA, and 40 (55%) according to GFI. Grade 3/4
toxicity related to chemotherapy was reported in 30 patients (42%) and
50% of CGA-frail patients experienced grade 3/4 toxicity, compared to
20% of CGA-fit patients (p�0.02). Grade 3/4 toxicity was experienced by
44% of GFI-frail patients, compared to 38% of GFI-fit patients (p�0.39).
After correcting for type of chemotherapy and age, toxicity was associated
with CGA-frailty (odds ratio (OR) 4.00, 95% confidence interval (CI)
1.77-13.59, p�0.03) while GFI-frailty was not associated with toxicity
(OR 1.11, 95% CI 0.85-1.46, p�0.43). Conclusions: In this randomized
study on first-line single-agent chemotherapy in elderly MBC patients,
baseline CGA demonstrated a good predictive value for grade 3/4 toxicity of
chemotherapy but GFI did not.
1082 General Poster Session (Board #25A), Sat, 8:00 AM-12:00 PM
Participation in adjuvant clinical breast cancer trials: Is there a difference
in survival compared to guideline adherent adjuvant treatment? A retrospective
multicenter cohort study of 5,326 patients. Presenting Author: Achim
Wöckel, Department of Gynecology and Obstetrics University Ulm, Ulm,
Germany
Background: Clinical trials (CT) usually compare a standard treatment
regime versus innovative new substances or regimens. However participation
in CT is available for only few patients and exclusion criteria is usually
very strict. Therefore this study tries to answer the following questions: (1)
Does participation in adjuvant CT improve survival in breast cancer (BC)?
(2) Is there a difference in survival compared to guideline adherence and
what is the role of the other treatments surrounding adjuvant breast cancer
treatment? Methods: This German multi-center [17 participating hospitals
all are certified as breast cancer centers] retrospective cohort study called
BRENDA (BRENDA � quality of breast cancer care under evidence-based
guidelines) included 5326 patients obtained from 1992 until 2005. The
definition of guideline adherence was based on the German national S3
guideline for diagnosis and treatment of breast cancer (2004). Results: 554
(10,4%) patients participated adjuvant clinical trials and 4772 (89,6%)
not. There was a trend towards a significantly impaired RFS [p�0.17;
HR�0.87 (95% CI: 0.71-1.06)] and OAS [p�0.65; HR�0.84 (95% CI:
0.65-1.09)] when comparing participants (PA) versus non-participants
(NPA). When stratifying for guideline adherence (compared to PA-guideline
conform in all adjuvant therapies) the outcome was not different in
NPA-guideline adherent [RFS: p�0.13; HR�1.25 (95% CI: 0.94-1.67)]
[OAS: p�0.83; HR�1.41 (95% CI: 0.96-2.06)]. However survival parameters
were significantly impaired in non-guideline conform PA [RFS:
p�0.005; HR�1.66 (95% CI: 1.16-2.38)] [OAS: p�0.01; HR�1.83
(95% CI: 1.15-2.92)] and non-guideline conform NPA [RFS: p�0,001;
HR�1.70 (95% CI: 1.27-2.26)] [OAS: p�0.002; HR�1.82 (95% CI:
1.24-2.67)]. Conclusions: There is a strong association between guideline
adherence in adjuvant treatment in BC and survival. PA in clinical trials
trended to an improved survival, but only if guideline adherent treatment
was applied. Patients who don�t have access to clinical seem to profit
substantially of guideline adherent adjuvant treatment.
Breast Cancer—Triple-Negative/Cytotoxics/Local Therapy
69s
1081 General Poster Session (Board #24H), Sat, 8:00 AM-12:00 PM
Sequential treatment with epirubicin/cyclophosphamide, followed by docetaxel
versus FEC120 in the adjuvant treatment of node-positive breast
cancer patients: Final survival analysis of the German ADEBAR phase III
study. Presenting Author: Wolfgang Janni, Universitätsklinikum Düsseldorf,
Department of Gynecology and Obstetrics, Duesseldorf, Germany
Background: Based on meta-analytic evidence, taxane containing adjuvant
chemotherapy has been established as standard treatment in breast cancer
(BC). However, in the MA-21 study, adriamycin-cyclophosphamide, followed
by paclitaxel was significantly inferior FEC120. We prospectively
compared a sequential epirubicin-docetaxel chemotherapy regimen to
FEC120. Methods: The ADEBAR study was a multicenter phase III trial
(n�1502) to evaluate whether pts with � 3 axillary lymph node metastases
BC benefit from a sequential anthracycline-docetaxel regimen (E90C–D: 4
cycles epirubicin [E] 90 mg/m2 plus cyclophosphamide [C] 600 mg/m2 q21d followed by 4 cycles docetaxel [D] 100mg/m2 q21d) compared to
dose-intensive anthracycline-containing polychemotherapy (FE120C: 6
cycles E 60 mg/m² d1�8, 5-FU 500mg/m² d1�8 and C 75 mg/m² d 1-14,
q4w). The observation time (median – 95%CI) was 49.5 (47.4 – 51.3) m.
Results: Treatment was stopped prematurely in 3.7% of the pts in the
E90C–D arm and in 8.0% in the FE120C arm due to toxicity (p�0.0009).
Antibiotic treatment was given in 10.4% (E90C–D) vs. 19.7% (FE120C), G-CSF support in 39.2% vs 61.4 % and erythropoietin stimulation in 8.7%
vs. 20.0%, respectively (p�0.0001). Haematological toxicity (leucopenia,
neutropenic fever, thrombocytopenia, anemia) was significantly higher in
the FEC-arm. At the time of the current analysis, 369 events of recurrence,
were observed: 166 events in the FE120C group and 193 in the E90C–D
group. The unadjusted hazard ratio (HR) was 0.877 (95 percent confidence
interval, 0.722 to 1.065; p�0.3819, log-rank test). Overall survival in the
two groups was not significantly different: (131 deaths with FEC vs. 134
with E90C–D (HR 0.996, 0.783-1.267, p�0.9691). Subgroup analyses,
stratifying for tumor size, lymph node involvement, hormone receptor and
HER2-neu status showed no significant difference between the two arms.
Conclusions: Different toxicity profiles given, hematological toxicity in the
FE120C group was more severe than in the E90C–D. In contrast to AC-P in
earlier studies, EC-Doc provides a feasible and effective option to FEC120.
1083 General Poster Session (Board #25B), Sat, 8:00 AM-12:00 PM
Randomized phase II study of two doses of pixantrone in patients with
metastatic breast cancer (N1031, Alliance). Presenting Author: Kostandinos
Sideras, Mayo Clinic, Rochester, MN
Background: Pixantrone (Pix) is a novel aza-anthracenedione with structural
similarities to mitoxantrone and promising activity against non-Hodgkin’s
lymphoma. Due to the lack of iron binding it is theorized to exhibit less
cardiotoxicity than the anthracyclines. Methods: N1031 is a phase II RCT of
2 schedules of Pix, in pts with MBC. Group A pts received 180mg/m2 IV q3
wks, and group B pts 85mg/m2 IV on days 1, 8, 15 q4 wks. Eligibility
included prior exposure to anthracyclines and/or taxanes, and 1 to 3
regiments in the metastatic setting (minimum of 2 if no prior adjuvant
therapy given). Due to lack of long term cardiac safety data no more than 12
cycles were allowed. Frequent cardiac imaging was performed per protocol.
Primary endpoint was RR and secondary endpoints included PFS, OS,
safety, and QOL. Planned sample size was 25 pts per group. Results: In
total 46 pts were evaluable (23 per group), mean age 55.5 yrs (range
38-79), 37% PS 0, 52% PS 1, and 11% PS 2. 80% of pts had prior
exposure to doxorubicin, 72% had prior (neo)-adjuvant therapy, 76% were
ER� and 57% received prior HT. Number of prior metastatic regiments
was: 1 (28%), 2 (61%) and 3 (11%). Most common adverse events (%) of
any grade were: alopecia (74), anemia (74), fatigue (85), nausea (67), ANC
decrease (87), and skin disorder (41). Grade 3-4 adverse events (%) at
least possibly attributed to Pix and occurring in at least 2 pts were: ANC
decrease (57), fatigue (9), increased AST (4%). One pt from each group
(4%) had a grade 3 decrease in EF. There were no major differences
between the two groups except for more oral mucositis in group A (35% vs
4%). Median number of cycles was 3 in group A (range 1-12) and 2 in
group B (range 1-8). There was only 1 confirmed tumor response per group
(4%,95% CI: 0.1-22%) prompting early termination of the trial. The
median PFS was 2.7 mo (95% CI: 1.8-3.8), and the median OS was 8.9 mo
(95% CI: 7.5-N/A). Conclusions: Pixantrone has insufficient activity in
patients with MBC exposed to prior anthracyclines and/or taxanes. Adverse
events were similar to prior experience with Pix. There were no major
differences between the 2 schedules of administration. There was no
significant cardiac toxicity seen in this trial. Correlative studies are
underway.
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