329P - Patient-reported outcomes (pros) from EMILIA, a phase 3 study of trastuzumab emtansine (T-DM1) vs capecitabine and lapatinib (XL) in HER2-positive l...

Date 29 September 2012
Event ESMO Congress 2012
Session Poster presentation I
Topics Anti-Cancer Agents & Biologic Therapy
Breast Cancer, Metastatic
Presenter Manfred Welslau
Authors M. Welslau1, V. Dieras2, J. Sohn3, S. Hurvitz4, D. Lalla5, L. Fang6, E. Guardino7, D. Miles8
  • 1Praxis Dr. Klausmann / Dr. Welslau, DE-63739 - Aschaffenburg/DE
  • 2Department Of Medical Oncology, Clinical Trial Unit, Institut Curie, 75005 - Paris/FR
  • 3Medical Oncology, Yonsei University College of Medicine, Seoul/KR
  • 4Medical Oncology, UCLA Jonsson Comprehensive Cancer Center and Translational Oncology Research International, Los Angeles/US
  • 5Biometrics, Health Outcomes And Payer Support, Genentech, South San Francisco/US
  • 6Biostatistics, Genentech, South San Francisco/US
  • 7Breast Medical Oncology, Genentech, Inc., South San Francisco/US
  • 8Medical Oncology, Mount Vernon Cancer Center, HA6 2 RN - Northwood/UK

Abstract

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; P<0.0001) and fewer grade 3/4 AEs (41% vs 57%) than those treated with XL. These gains in efficacy and safety were accompanied by improvements in patient-reported health status in the 450 T-DM1 and 445 XL PRO-evaluable pts. T-DM1 pts maintained stable FACT-B TOI scores longer than XL pts (time to TOI worsening 7.1 vs 4.6 months; HR=0.796). A comparison in FACT-B subscales between treatment arms will be presented. From cycle 2 through 8, more pts in the XL arm than in the T-DM1 arm reported diarrhea symptoms such as having >1 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.