التفاصيل البيبلوغرافية
| العنوان: |
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. |
| المؤلفون: |
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 |
| المصدر: |
JAMA: Journal of the American Medical Association; 1/3/2017, Vol. 317 Issue 1, p37-47, 11p, 1 Diagram, 5 Charts |
| مصطلحات موضوعية: |
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 |
| مستخلص: |
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. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
