P1-12-02: Patient-Reported Outcomes (PROs) from a Randomized Phase II Study (TDM4450g/BO21976) of Trastuzumab Emtansine (T-DM1) vs Trastuzumab Plus Docetaxel (HT) in Previously Untreated HER2−Positive Metastatic Breast Cancer (MBC).
Authors: Bianchi GV , Kocsis J , Dirix L , Torigoe Y , Lalla D , Tong YB , Guardino AE , Hurvitz SA 
Published: June 2012

Abstract
Background: T-DM1 is an antibody-drug conjugate in development for HER2−positive cancer. As a single-agent, it has demonstrated promising efficacy and safety when administered after multiple lines of HER2−directed therapy. In the current study, we compared the safety and efficacy of T-DM1 to standard first-line treatment for HER2−positive MBC. This abstract highlights the PRO results in the context of efficacy and safety.
Methods: Patients with HER2−positive MBC and no prior MBC therapy were randomized 1:1 to T-DM1 3.6 mg/kg IV q3w or H 6 mg/kg IV (8 mg/kg in cycle 1) + T 75 or 100 mg/m2 IV q3w. Primary objectives were investigator-assessed progression free survival (PFS) and safety. Key secondary end points included objective response rate and the FACT-B Trial Outcome Index (TOI). Patients completed the FACT-B on day 1 of each treatment cycle. The FACT-B TOI, the primary PRO end point, comprises a subset of the FACT-B and provides a summary measure of physical and functional well being and breast cancer specific symptoms. Time to FACT-B TOI worsening (ie, ≥5 point decrease in TOI) was assessed with Kaplan-Meier methods and a Cox model. A repeated measures mixed effects (RMME) model was used to evaluate potential treatment effects on TOI across cycles. Preliminary PRO results based on a data cutoff of November 15, 2010, are included here; final data will be presented.
Results: A total of 137 patients were randomized (67 T-DM1, 70 HT). Baseline patient and disease characteristics were similar in each arm. Patients treated with T-DM1 had longer PFS (14.2 vs 9.2 months, HR=0.59, P= 0.035) with less toxicity (eg, 46.4% grade 3/4 adverse events with T-DM1 vs 89.4% with HT) than those treated with HT. ORR was similar in both arms (64.2% T-DM1, 58.0% HT). A total of 132 patients (65 T-DM1, 67 HT) were evaluable for PRO analyses with a high compliance rate. In a preliminary analysis, FACT-B TOI worsening was significantly delayed in the T-DM1 arm compared with the control arm (7.5 vs 3.5 months, HR=0.58, P=0.022). The RMME model showed a mean difference of 3.65 in FACT-B TOI scores (P=0.023), mainly driven by physical well being (PWB) scores (mean difference 2.28, P=0.002), favoring T-DM1. In addition, 5 of 7 PWB items showed significantly better mean scores in the T-DM1 arm: “lack of energy” (P=0.011), “trouble meeting needs of family” (P=0.025), “bothered by side effects” (P&lt;0.001), “feeling ill” (P=0.016) and “forced to spend time in bed” (P=0.015); the 2 remaining items, “nausea” and “pain,” showed numerically better mean scores with T-DM1.
Conclusions: Compared to HT, T-DM1 as first-line treatment of HER2−positive MBC conferred longer PFS and a more favorable toxicity profile. The PRO data suggest that T-DM1 is also associated with meaningfully improved tolerability relative to HT, contributing to an overall clinical benefit and better health-related quality of life. Thus, T-DM1 may improve the standard of care for patients with previously untreated HER2−positive MBC.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-12-02.