Rugo, Hope S. and Barve, Abhijit and Waller, Cornelius F. and Hernandez-Bronchud, Miguel and Herson, Jay and Yuan, Jinyu and Sharma, Rajiv and Baczkowski, Mark and Kothekar, Mudgal and Loganathan, Subramanian and Manikhas, Alexey and Bondarenko, Igor and Mukhametshina, Guzel and Nemsadze, Gia and Parra, Joseph D and Abesamis Tiambeng, Maria Luisa T. and Baramidze, Kakhaber and Akewanlop, Charuwan and Vynnychenko, Ihor and Sriuranpong, Virote and Mamillapalli, Gopichand and Ray, Sirshendu and Ruiz, Eduardo P Yanez and Pennella, Eduardo (2017) 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. JAMA, 317 (1). pp. 37-47.
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JAMA paper of Proposed Trastuzumab Biosimilar by Hope R et al 2016.pdf Download (451kB) | Preview |
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 (n = 230) or trastuzumab (n = 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
| Item Type: | Article |
|---|---|
| Additional Information: | JAMA. doi:10.1001/jama.2016.18305 |
| Subjects: | Oncology |
| Depositing User: | Елена Шрамко |
| Date Deposited: | 12 Sep 2017 08:49 |
| Last Modified: | 12 Sep 2017 08:50 |
| URI: | http://repo.dma.dp.ua/id/eprint/1935 |
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