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

598^ General Poster Session (Board #9A), Sat, 8:00 AM-12:00 PM
Quality of life assessment in CLEOPATRA, a phase III study combining
pertuzumab with trastuzumab and docetaxel in metastatic breast cancer.
Presenting Author: Javier Cortes, Department of Oncology, Vall d’Hebron
University Hospital, Barcelona, Spain
Background: CLEOPATRA compared the efficacy and safety of the HER2
dimerization inhibitor pertuzumab (P) plus trastuzumab (T) and docetaxel
(D) with placebo (Pla)�T�D in HER2-positive 1st-line MBC. Pts in both
arms received a median of 8 cycles of D; Pla/P�T was continued until
progressive disease (PD). The safety profile in both arms was similar with a
substantial decrease in adverse events (AEs) once chemotherapy finished.
The independently assessed progression-free survival was significantly
improved with P�T�D compared with Pla�T�D; objective response and
duration of response were also improved with P�T�D (Baselga NEJM
2012). Here we report health-related quality of life (HRQoL) data from
CLEOPATRA. Methods: Time to deterioration of HRQoL was evaluated using
the FACT-B questionnaire and defined as decrease from baseline (BL) of
�5 points in the TOI-PFB subscale score. Female pts completed questionnaires
every 3rd cycle of therapy within 3 days before each tumor
assessment until independently determined PD. An exploratory analysis
investigated time to deterioration in breast cancer symptoms and functions.
Results: 56.7% (Pla�T�D) and 59.5% (P�T�D) of pts experienced
deterioration of HRQoL during the study based on TOI-PFB. The median
time to deterioration was 18.3 vs 18.4 wks (~6 cycles) (HR 0.97; P �
.7161). At Cycle 6, the mean reduction in TOI-PFB score from BL was –3.5
(Pla�T�D) vs –3.0 (P�T�D). At subsequent cycles, when most pts had
discontinued D, mean reductions were smaller, suggesting that after an
early decline patients’ scores improved slightly. Overall, mean changes
were small in both arms. Compliance with completion of the FACT-B
questionnaire was �75% beyond the 1st year in both arms. An exploratory
analysis suggested that time to deterioration in BCS score, which measures
symptoms and issues relevant in breast cancer, was delayed with P�T�D
(18.3 vs 26.7 wks; HR 0.77; P � .0061). Conclusions: Combining P with
T�D appears to have no detrimental effect on HRQoL. Results suggest that
P�T�D is associated with a substantial delay in the time to deterioration in
BCS score as would be expected given the improved efficacy and the low
incidence of AEs once D is discontinued.
600 General Poster Session (Board #9C), Sat, 8:00 AM-12:00 PM
Trastuzumab-related cardiotoxicity among older breast cancer patients.
Presenting Author: Mariana Chavez-Mac Gregor, University of Texas M. D.
Anderson Cancer Center, Houston, TX
Background: The use of trastuzumab in the adjuvant setting is associated
with reduction in mortality and recurrence. Although trastuzumab is
extremely well tolerated, its use is associated with congestive heart failure
(CHF). The incidence of this complication in the general population
remains largely unknown, especially in older patients. In this study we
evaluated the rates and risk factors associated with trastuzumab-related
CHF in a large cohort of older breast cancer patients. Methods: Breast
cancer patients � 66 years with full Medicare coverage, diagnosed with
stage I-III breast cancer between 2005-2007, and treated with chemotherapy
were identified in the Surveillance, Epidemiology and End Results-
Medicare (SEER-Medicare) database. Chemotherapy and trastuzumab use,
comorbidities and CHF were identified using ICD-9 and HCPCS codes.
Analyses included descriptive statistics, Cox proportional hazard model
using trastuzumab as a time-dependent variable and logistic regression.
Results: A total of 3,983 patients were included, 847 (21.7%) of them
received trastuzumab, median age of the entire cohort was 71 years old.
Among trastuzumab users the rate of CHF was 28.6% compared to 18.1%
in non-trastuzumab users (p�.0001). After adjusting for demographic and
clinical characteristics, comorbidities, and type of chemotherapy used,
trastuzumab users were more likely to develop CHF than non-trastuzumab
users (HR 1.74; 95% CI 1.47-2.06). Among trastuzumab users, older age
did not further increase the risk, however history of coronary artery disease
(OR 2.23; 95%CI 1.56-3.19), heart valve disease (OR 1.41; 95%CI
1.41-2.88) and emphysema -as a proxy for smoking- (OR 2.03; 95% CI
1.13-3.63) significantly increased the risk of CHF. There was a trend for
increased risk of CHF associated with anthracycline use (OR 1.36; 95% CI
0.93-2.00). Conclusions: In this large cohort of older breast cancer
patients, the risk of CHF among trastuzumab users was 1.74 times higher
than non-trastuzumab users, which is higher than what has been reported
in younger clinical trial participants. Among older breast cancer patients
treated with trastuzumab, cardiac comorbidities and emphysema may
identify high risk patients.
Breast Cancer—HER2/ER
31s
599 General Poster Session (Board #9B), Sat, 8:00 AM-12:00 PM
Impact of hormone receptor (HR) status on clinicopathological features,
patterns of recurrence, and clinical outcomes among patients (pts) with
human epidermal growth factor receptor-2 positive (HER2) breast cancer
(BC) in the National Comprehensive Cancer Network (NCCN). Presenting
Author: Ines Maria Vaz Duarte Luis, Dana-Farber Cancer Institute, Boston,
MA
Background: According to gene expression profiling, HER2� BC is heterogeneous
and appears to diverge by HR status. Methods: We evaluated 3394
pts who presented to NCCN centers with stage I-III HER2� BC between
2000-07. Pts were classified as HR� (ER� and/or PR�) and HR- (ER- and
PR-). Chi-square, univariate logistic regression, log-rank test, and Cox
hazard proportional regression were used for analysis. Results: Median
follow-up was 51 months. 59% of patients had HR� and 41% HR- disease
respectively. Pts with HR- BC were more likely to be postmenopausal and to
present with higher stage and high grade disease (p�0.001). Most pts
received adjuvant or neoadjuvant therapy; 44% received adjuvant trastuzumab.
Recurrences were recorded for 458 pts. HR- patients were more
likely to recur first in the central nervous system (CNS) (OR: 1.8, 95% CI:
1.1, 2.9; p� 0.03) and less likely to recur in bone (OR: 0.5, 95% CI: 0.3,
0.8; p�0.01). No differences in risk of lung or liver recurrence were
observed. Combining first and subsequent sites of recurrence, the difference
in CNS involvement was lost (p�0.107) but HR- were more likely to
experience lung involvement (OR: 1.5, 95% CI: 1.0, 2.2; p� 0.05). After
adjusting for age, year of diagnosis (y), race, stage, and grade, HR- had
worse survival after initial BC diagnosis than HR� pts (Hazard Ratio of
death [HRd] 1.4, 95% CI: 1.14, 1.7; p�0.01). However, the risk of death
was not proportional over time with HR- having significantly increased
hazard in the first five years: HRd 0-2 y 1.9 [1.3, 2.9]; p� 0.01; HRd 2-5y
1.5, [1.2, 2.0]; p�0.01; HRd 5� y, 0.8, [ 0.6, 1.2], p�0.29. Conclusions:
Clinicopathological features, sites of recurrence, and risk of death over time
for HER2� BC differed by HR status. This suggests that HR status in
HER2� BC is clinically relevant. These differences should be further
explored from a mechanistic and therapeutic standpoint.
601 General Poster Session (Board #9D), Sat, 8:00 AM-12:00 PM
Impact of adjuvant trastuzumab-based chemotherapy in T1ab nodenegative
HER2 overexpressing breast carcinomas. Presenting Author:
Jean-Sebastien Frenel, Institut de Cancerologie de l’Ouest/Site Rene
Gauducheau, Saint-Herblain, France
Background: HER2 overexpression has been recognized as a pejorative
prognostic factor in node negative T1ab (T1abN0) breast tumors. Randomized
clinical trials have shown benefit of adjuvant trastuzumab-based
chemotherapy (ATBC) for node-positive and/or greater than 1 cm (T1c or
more) HER2� breast carcinomas. There are no prospective efficacy data of
ATBC in T1abN0 HER2� tumors. Methods: We retrospectively evaluated
276 cases of T1ab node-negative HER2� breast tumors in 8 French
Comprehensive Cancer Centers. We assessed clinical, therapeutic features
and outcome. We estimated the probability of disease-free survival (DFS),
analyzed associations of ATBC, patient and tumor characteristics with DFS
and prognosis factors using the log-rank test, multivariate analysis with
logistic regression and Cox’s proportional hazards model. Results: Out of the
276 T1abN0 cases, 129 (47%) received ATBC (ATBC�) and 123 (45%)
were not treated by either trastuzumab or chemotherapy (ATBC-). Of these
252 ATBC� or ATBC- patients, decision of ATBC was associated with date
of diagnosis (before or after ASCO 2005 Annual Meeting when interim
results from three trastuzumab adjuvant trials were reported) and with poor
prognosis features: negative hormone receptors (HR-) status, Elston-Ellis
high grade, tumor size � 5 mm and age. With a median follow-up of 44
months 16 recurrences were observed (13 in the ATBC- group, 2 in the
ATBC� and 1 with adjuvant chemotherapy alone). Nine recurrences were
distant metastases. A survival benefit in ATBC� was observed with a 99%
40-months DFS versus 93% for ATBC- (logrank p-test � 0.018). In an
exploratory analysis, two factors were significantly associated with worst
prognosis for ATBC- that were not observed for ATBC� : HR- status (98%
40-months DFS for ATBC� patients versus 84% for ATBC- patients;
logrank p-test � 0.0003) and presence of lymphovascular invasion (100%
40-months DFS for ATBC� versus 73% in ATBC- cases; logrank p-test �
0.003). Conclusions: In our seriesATBC is associated with a significant
reduction of risk of recurrence of T1abN0 HER2� tumors. A clear DFS
benefit of ATBC was observed in HR- tumors and/or in presence of
lymphovascular invasion.
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