Final overall survival analysis of the phase 3 HERITAGE study demonstrates equivalence of trastuzumab-dkst to trastuzumab in HER2-positive metastatic breast cancer

Abstract

Purpose: The phase 3 HERITAGE trial demonstrated that the biosimilar trastuzumab-dkst is well tolerated with similar efficacy (measured by overall response rate [ORR] and progression-free survival [PFS]) compared with originator trastuzumab combined with taxane followed by monotherapy in patients with HER2-positive metastatic breast cancer (MBC). Herein, we present final overall survival (OS) from HERITAGE.

Methods: HERITAGE is a multicenter, double-blind, randomized, parallel-group study. Patients were randomized 1:1 to receive trastuzumab-dkst or trastuzumab plus taxane followed by continued monotherapy until disease progression. Overall survival was to be assessed at 36 months or after 240 deaths, whichever occurred first, as observed from time of randomization of last patient.

Results: At the final analysis (36 months), 242 patients in the intention-to-treat population had died during the study: 116 and 124 in the trastuzumab-dkst and trastuzumab groups, respectively, and 1 untreated patient from each treatment group. Median OS by Kaplan-Meier analysis was 35.0 months with trastuzumab-dkst and 30.2 months with trastuzumab. Evaluation of PFS showed a median of 11.1 months in both treatment groups. No new safety concerns were reported from week 48 until the end of the survival follow-up.

Conclusion: This is the first phase 3 trial of a trastuzumab biosimilar to report long-term survival data similar to originator trastuzumab in patients with MBC. The comparable long-term OS between the trastuzumab-dkst and originator trastuzumab groups further supports the similarity of trastuzumab-dkst with originator trastuzumab and establishes trastuzumab-dkst as a safe and effective treatment option for patients with HER2-positive MBC. ClinicalTrials.gov NCT02472964; 6/16/2015.

Keywords: Biosimilar; Metastatic breast cancer; Overall survival; Trastuzumab.

Conflict of interest statement

HS Rugo has received travel, accommodations, and expenses from Amgen, Merck, Viatris Inc, Pfizer, and Puma Biotechnology and research funding (provided to the Regents of the University of California) from Eisai, Genentech/Roche, Lilly, Macrogenics, Merck, Novartis, OBI Pharma, Daiichi, Immunomedics, and Pfizer. EJ Pennella was a paid employee of Mylan Inc (now Viatris Inc) during the time of the study and may hold stock with the company. U Gopalakrishnan, K Beckmann, HF Koch, A Barve, and A Fuentes-Alburo are paid employees of Viatris Inc and may hold stock with the company. M Hernandez-Bronchud has served as a consultant/advisory board member for Viatris Inc. S Loganathan, S Deodhar, and A Marwah are paid employees of Biocon Research Ltd and may hold stock with the company. C Akewanlop has received travel, accommodations, and expenses from Amgen, AstraZeneca, Roche, and Bristol-Myers Squibb. CF Waller is a consultant/advisory board member for Viatris Inc. J Herson, A Manikhas, I Bondarenko, G Mukhametshina, G Nemsadze, JD Parra, MLT Abesamis-Tiambeng, K Baramidze, I Vynnychenko, V Sriuranpong, G Mamillapalli, S Roy, and EP Yanez Ruiz have nothing to disclose.

Figures

Fig. 1

Patient CONSORT diagram for the intention-to-treat population in the HERITAGE trial

Fig. 2

Kaplan–Meier plot of overall survival at the final assessment in the intention-to-treat population based on central tumor evaluation. Numbers of patients at risk are displayed at the bottom of the figure. The stratified hazard was calculated by assigned taxane, tumor progression, and tumor endocrine status

Fig. 3

Kaplan–Meier plot of progression-free survival at the final assessment in the intention-to-treat population based on central tumor evaluation. Numbers of patients at risk are displayed at the bottom of the figure. The stratified hazard was calculated by assigned taxane, tumor progression, and tumor endocrine status