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absolute difference of median values. Linear regression analysis was also conducted
to predict the effects of a new anticancer drug on OS on the basis of its effects on
PFS.
Results: A total of 5041 studies were identified and 144 fulfilled the eligibility
criteria. Selected studies included 315 treatment arms, which represents 43,459
patients with mBC. There was a significant relationship between median PFS and
median OS across included trials (r = 0.428; p < 0.01). The correlation between
median PFS/TTP and median OS was higher for studies evaluating chemotherapy
alone (r = 0.575; p ≤ 0.01) or in combination (r = 0.632; p ≤ 0.01) compared with
those evaluating hormone therapy (non-significant r). The correlation coefficient for
the treatment effect on PFS and OS was estimated at 0.427 (p < 0.01). The linear
regression equation was: ΔOS = -0.088 (95% CI, -1.347 to 1.172) + 1.753 (95% CI,
1.307 to 2.198) * ΔPFS, with a proportion of variation explained (R 2 ) of 0.86. Results
of the regression analysis predict that a difference in median PFS/TTP of 5, 10, 15,
and 20 months would translate into a difference in median OS of 8.7, 17.4, 26.2, and
35.0 months respectively.
Conclusion: The present findings point toward a statistically significant correlation
between PFS and OS in the context of mBC and support the surrogacy of PFS for OS
in this cancer setting.
Disclosure: All authors have declared no conflicts of interest.
329P PATIENT-REPORTED OUTCOMES (PROS) FROM EMILIA, A
PHASE 3 STUDY OF TRASTUZUMAB EMTANSINE (T-DM1) VS
CAPECITABINE AND LAPATINIB (XL) IN HER2-POSITIVE
LOCALLY ADVANCED OR MBC
M. Welslau, 1 , V. Diéras2 , J. Sohn3 , S. Hurvitz4 , D. Lalla5 , L. Fang6 , E. Guardino7 ,
D. Miles8 1
Medical Office Hematology, Praxis Dr. Klausmann / Dr. Welslau, Aschaffenburg,
GERMANY, 2 Department of Medical Oncology, Clinical Trial Unit, Institut Curie,
Paris, FRANCE, 3 Medical Oncology, Yonsei University College of Medicine,
Seoul, KOREA, 4 Medical Oncology, UCLA Jonsson Comprehensive Cancer
Center and Translational Oncology Research International, Los Angeles, CA,
UNITED STATES OF AMERICA, 5 Health Outcomes, Genentech, South San
Francisco, CA, UNITED STATES OF AMERICA, 6 Biostatistics, Genentech, South
San Francisco, CA, UNITED STATES OF AMERICA, 7 Breast Medical Oncology,
Genentech, Inc., South San Francisco, CA, UNITED STATES OF AMERICA,
8
Medical Oncology, Mount Vernon Cancer Center, Northwood, UNITED
KINGDOM
Background: The antibody-drug conjugate T-DM1 combines the antitumor activities
of trastuzumab (T) with intracellular delivery of the cytotoxic agent DM1. In the
EMILIA study, the efficacy and safety of T-DM1 was compared to XL. Here we
report the PRO results.
Methods: Pts with centrally confirmed HER2-positive MBC and prior therapy with
T and a taxane were randomized to T-DM1 or XL administered in 21-day cycles. Pts
completed the FACT-B, a 37-item questionnaire composed of 5 subscales at baseline
and on day 1 every 2 cycles until disease progression (PD), 6 wks after PD and every
3 mos thereafter. A 24-item subset of FACT-B, the Trial Outcome Index (TOI)
provides a summary of physical and functional well-being and breast cancer-specific
symptoms. Time to FACT-B TOI worsening (ie, ≥5 point decrease in TOI), the main
PRO analysis, was assessed by Kaplan-Meier methods and a Cox model in female pts
with baseline and ≥1 post-baseline TOI score. An exploratory PRO end point was
the incidence of symptoms measured by the Diarrhea Assessment Scale (DAS), in
which pts rated diarrhea symptoms in 4 domains (frequency, urgency, discomfort,
stool consistency) on a 4-point scale at baseline and on day 1 of each cycle until PD.
Results: Pts treated with T-DM1 had longer PFS (9.6 vs 6.4 months; HR=0.650;
P1 stool per day
(57% vs 30%); loose or watery stools (70% vs 37%); somewhat to very urgent stools
(54% vs 26%) and mild-moderate to very severe abdominal discomfort with bowel
movements (45% vs 25%).
Conclusions: Improvements in efficacy and safety were accompanied by, clinically
significant benefits in health-related quality of life in pts treated with T-DM1 vs XL.
Keywords: diarrhea, T-DM1, patient-reported outcomes, HER2-positive.
Disclosure: V. Diéras: *Compensated consultant/advisory relationship with
Genentech/Roche, Novartis, Sanofi, Amgen, Clovis, Pfizer, GSK *Honoraria from
Genentech/Roche, Novartis, Sanofi, Amgen, Clovis, Pfizer, GSK J. Sohn: Research
funding from Roche, Amgen and GSKS. Hurvitz: *Support for study-related travel
from Roche *Research funding for institution from Roche D. Lalla: Genentech
employee, owns Roche stockL. Fang: Genentech employee, owns Roche stockE.
Guardino: Genentech employee, owns Roche stock All other authors have declared
no conflicts of interest.
Annals of Oncology
330P QUALITY OF LIFE (QOL) ASSESSMENT IN WOMEN WITH
LOCALLY ADVANCED (LA) OR METASTATIC BREAST CANCER
(MBC): RESULTS OF A PHASE II TRIAL WITH ERIBULIN
W.R. Simons 1 , J. Cortes 2
1 Global Health Technology Assessment, Eisai, Inc., Woodcliff Lake, NJ, UNITED
STATES OF AMERICA, 2 Breast Cancer Program, Vall d’Hebron University
Hospital, Barcelona, SPAIN
Objective: Eribulin is a nontaxane microtubule dynamics inhibitor with a
mechanism of action different from many other tubulin targeting agents and
indicated for monotherapy treatment of patients with LA or MBC who have
progressed after at least an anthracycline and a taxane. While eribulin has shown
overall survival and extended progression free periods benefits in these women, QoL
associated with those benefits need to be determined.
Methods: We use a Phase II clinical trial where 291 women with LA or MBC were
required to have received prior treatment with an anthracycline, a taxane, and
capecitabine. Eribulin was administered at 1.23 mg/m 2 (equivalent to 1.4mg/m 2
eribulin mesilate) i.v. over 2 to 5 minutes on Days 1 and 8 of a 21-day cycle.
EORTC-QLQ-BR32 was administered every second cycle, before drug administration
and before patients were informed of their tumor assessment. As these data are
repeated observations, every second cycle, across the course of treatment, generalized
estimating equations (GEE) were applied to individual QOL scores with response,
complete or partial tumor response as well as progressive disease as independent
indicators.
Results: Two-hundred eighty three women provided a total of 1068 QOL
assessments. Their general health status was 68.88 (P < 0.0001) on a 100 point scale,
improving by 7.90 (P = 0.0153) when responding to eribulin. Indeed, women
responding to eribulin improved in each of the subscale domains, including
emotional functioning (10.54; P = 0.0004), physical functioning (12.95; P = 0.0008),
role functioning (9.37; P =0.0005), pain (7.90; P = 0.0153) and breast symptoms
(-12.42; P = 0.0004). Hair loss was a concern, (-9.18; P = 0.0001). Conversely,
progressive disease significantly worsens their QOL, physical functioning by (-19.18;
P < 0.0001), role functioning (-9.36; P < 0.0001) and emotional functioning (-10.459;
P < 0.0001).
Conclusion: LABC or MBC significantly impacts every aspect of these women’s lives
as measured by the EORTC-QLQ-BR32 questionnaire. While hair loss was a
concern, eribulin provided these women with significant relief and measureable and
meaningful improvements in overall QOL, including emotional, social, role
functioning subscales and pain and breast symptoms.
Disclosure: W.R. Simons: W. Robert Simons is an Eisai Inc employee. All other
authors have declared no conflicts of interest.
331P IMPACT OF RESPONSE SHIFT ON TIME TO QUALITY OF LIFE
SCORES DETERIORATION IN BREAST CANCER PATIENTS: IS
IT TIME TO MOVE FOR QOL RECIST CRITERION?
Z. Hamidou 1 , T.S. Dabakuyo 1 , F. Guillemin 2 , T. Conroy 3 , M. Velten 4 , D. Jolly 5 ,
M. Mercier 6 , S. Causeret 7 , J. Cuisnier 7 , F. Bonnetain 1
1 Biostatistic and Epidemiological Unit(ea 4184), Centre Georges François
Leclerc, Dijon, FRANCE, 2 Clinical Epidemiology and Evaluation Department,
CIC-EC, Nancy, FRANCE, 3 Oncology, Centre Alexis Vautrin, Vandoeuvre Les
Nancy Cedex, FRANCE, 4 Epidemiology and Public Health Laboratory, College of
Medicine, Strasbourg, FRANCE, 5 Création du Pôle Recherche et Innovations,
University Hospital, Reims, FRANCE, 6 Cellular and Molecular Biology Laboratory
EA 3181, University Hospital of Besançon, Besançon, FRANCE, 7 Surgery,
Centre Georges François Leclerc, Dijon, FRANCE
Background: Time to quality of life (QoL) score deterioration (TD) is a method of
longitudinal QoL data analysis that has been proposed for breast cancer (BC)
patients (Hamidou et al Oncologist 2011). As for RECIST criteria, the optimal
definitions dealing with reference should be explored. This study aims to study the
impact of changes in internal standards (CIS) of response-shift (RS) and the
influence of baseline QoL expectancies on TD.
Methods: A prospective multicenter study including all women hospitalized for a
primary BC was conducted. The EORTC-QLQ-C30 and BR-23 questionnaires were
used to assess the QoL at baseline, at the end of 1 st hospitalization, and 3 and 6
months after. CIS was investigated by the then-test method. QoL expectancy was
assessed at baseline using Likert scale. Deterioration was defined as a decrease in
QoL scores reaching at least the mean difference identified as minimal clinically
important difference (MCID) using Jaeschke’s transition question. Sensitivity analyses
were done using the then-test score as reference score, and considering 5 and 10
points as MCID. TD was estimated using Kaplan-Meier method. Cox regression
analyses were used to identify factors influencing TD.
Results: From February 2006 to February 2008, 381 women were included. For role
functioning dimension, the median TD increased from 3.2 months [95% CI:
3.1-3.36] to 4.76 months [3.3-6.2] when adjusting on CIS. For body image when
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