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JAMA. 2017 Jan 3;317(1):37-47. doi: 10.1001/jama.2016.18305.

Effect of a Proposed Trastuzumab Biosimilar Compared With Trastuzumab on Overall Response Rate in Patients With ERBB2 (HER2)-Positive Metastatic Breast Cancer: A Randomized Clinical Trial.

Author information

1
University of California San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco.
2
Biocon Research Limited, Bangalore, India3Now with Mylan Inc, Canonsburg, Pennsylvania.
3
Department of Haematology, Oncology, and Stem Cell Transplantation, University Medical Centre Freiburg and Faculty of Medicine, University of Freiburg, Freiburg, Germany.
4
Quiron-Dexeus, Barcelona, Spain.
5
Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland.
6
Mylan Inc, Canonsburg, Pennsylvania.
7
Biocon Research Limited, Bangalore, India.
8
City Clinical Oncology Dispensary, Saint Petersburg, Russia.
9
Dnipropetrovsk State Medical Academy, Dnipropetrovsk, Ukraine.
10
Regional Clinical Oncological Center, Kazan, Russia.
11
Institute of Clinical Oncology, Tbilisi, Georgia.
12
St Luke's Medical Center Global City, Taguig City, Philippines.
13
Cardinal Santos Medical Center, Manila, Philippines.
14
Golden Fleece 21 Century Health House Ltd, Tbilisi, Georgia.
15
Siriraj Hospital, Bangkok, Thailand.
16
Sumy State University, Sumy, Ukraine.
17
King Chulalongkorn Memorial Hospital, Chulalongkorn University, Bangkok, Thailand.
18
City Cancer Center, Vijayawada, India.
19
Curie Manavata Cancer Centre, Nasik, India.
20
Instituto Clinico Oncologico del Sur, Temuco, Chile.

Abstract

Importance:

Treatment with the anti-ERBB2 humanized monoclonal antibody trastuzumab and chemotherapy significantly improves outcome in patients with ERBB2 (HER2)-positive metastatic breast cancer; a clinically effective biosimilar may help increase access to this therapy.

Objective:

To compare the overall response rate and assess the safety of a proposed trastuzumab biosimilar plus a taxane or trastuzumab plus a taxane in patients without prior treatment for ERBB2-positive metastatic breast cancer.

Design, Setting, and Participants:

Multicenter, double-blind, randomized, parallel-group, phase 3 equivalence study in patients with metastatic breast cancer. From December 2012 to August 2015, 500 patients were randomized 1:1 to receive a proposed biosimilar or trastuzumab plus a taxane. Chemotherapy was administered for at least 24 weeks followed by antibody alone until unacceptable toxic effects or disease progression occurred.

Interventions:

Proposed biosimilar (nā€‰=ā€‰230) or trastuzumab (nā€‰=ā€‰228) with a taxane.

Main Outcomes and Measures:

The primary outcome was week 24 overall response rate (ORR) defined as complete or partial response. Equivalence boundaries were 0.81 to 1.24 with a 90% CI for ORR ratio (proposed biosimilar/trastuzumab) and -15% to 15% with a 95% CI for ORR difference. Secondary outcome measures included time to tumor progression, progression-free and overall survival at week 48, and adverse events.

Results:

Among 500 women randomized, the intention-to-treat population included 458 women (mean [SD] age, 53.6 [11.11] years) and the safety population included 493 women. The ORR was 69.6% (95% CI, 63.62%-75.51%) for the proposed biosimilar vs 64.0% (95% CI, 57.81%-70.26%) for trastuzumab. The ORR ratio (1.09; 90% CI, 0.974-1.211) and ORR difference (5.53; 95% CI, -3.08 to 14.04) were within the equivalence boundaries. At week 48, there was no statistically significant difference with the proposed biosimilar vs trastuzumab for time to tumor progression (41.3% vs 43.0%; -1.7%; 95% CI, -11.1% to 6.9%), progression-free survival (44.3% vs 44.7%; -0.4%; 95% CI, -9.4% to 8.7%), or overall survival (89.1% vs 85.1%; 4.0%; 95% CI, -2.1% to 10.3%). In the proposed biosimilar and trastuzumab groups, 239 (98.6%) and 233 (94.7%) had at least 1 adverse event, the most common including neutropenia (57.5% vs 53.3%), peripheral neuropathy (23.1% vs 24.8%), and diarrhea (20.6% vs 20.7%).

Conclusions and Relevance:

Among women with ERBB2-positive metastatic breast cancer receiving taxanes, the use of a proposed trastuzumab biosimilar compared with trastuzumab resulted in an equivalent overall response rate at 24 weeks. Further study is needed to assess safety and long-term clinical outcome.

Trial Registration:

clinicaltrials.gov Identifier: NCT02472964; EudraCT Identifier: 2011-001965-42.

PMID:
27918780
DOI:
10.1001/jama.2016.18305
[Indexed for MEDLINE]

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