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- Title
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.
- Authors
Rugo, Hope S.; Barve, Abhijit; Waller, Cornelius F.; Hernandez-Bronchud, Miguel; Herson, Jay; Jinyu Yuan; Sharma, Rajiv; Baczkowski, Mark; Kothekar, Mudgal; Loganathan, Subramanian; Manikhas, Alexey; Bondarenko, Igor; Mukhametshina, Guzel; Nemsadze, Gia; Parra, Joseph D.; Abesamis-Tiambeng, Maria Luisa T.; Baramidze, Kakhaber; Akewanlop, Charuwan; Sriuranpong, Virote; Mamillapalli, Gopichand
- Abstract
<bold>Importance: </bold>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.<bold>Objective: </bold>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.<bold>Design, Setting, and Participants: </bold>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.<bold>Interventions: </bold>Proposed biosimilar (n = 230) or trastuzumab (n = 228) with a taxane.<bold>Main Outcomes and Measures: </bold>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.<bold>Results: </bold>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%).<bold>Conclusions and Relevance: </bold>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.<bold>Trial Registration: </bold>clinicaltrials.gov Identifier: NCT02472964; EudraCT Identifier: 2011-001965-42.
- Subjects
HER2 gene; BREAST cancer treatment; TRASTUZUMAB; TREATMENT effectiveness; CANCER chemotherapy; THERAPEUTICS; BIOTHERAPY; ANTINEOPLASTIC agents; BIOLOGICAL products; BREAST tumors; CELL receptors; COMPARATIVE studies; HYDROCARBONS; RESEARCH methodology; MEDICAL cooperation; PACLITAXEL; RESEARCH; RESEARCH ethics; SURVIVAL analysis (Biometry); TIME; EVALUATION research; RANDOMIZED controlled trials; DISEASE remission; BLIND experiment; DISEASE progression
- Publication
JAMA: Journal of the American Medical Association, 2017, Vol 317, Issue 1, p37
- ISSN
0098-7484
- Publication type
journal article
- DOI
10.1001/jama.2016.18305