دورية أكاديمية
Cobimetinib combined with vemurafenib in advanced BRAF(V600)-mutant melanoma (coBRIM): updated efficacy results from a randomised, double-blind, phase 3 trial.
| العنوان: | Cobimetinib combined with vemurafenib in advanced BRAF(V600)-mutant melanoma (coBRIM): updated efficacy results from a randomised, double-blind, phase 3 trial. |
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| المؤلفون: | Ascierto, PA, McArthur, GA, Dréno, B, Atkinson, V, Liszkay, G, Di Giacomo, AM, Mandalà, M, Demidov, L, Stroyakovskiy, D, Thomas, L, de la Cruz-Merino, L, Dutriaux, C, Garbe, C, Yan, Y, Wongchenko, M, Chang, I, Hsu, JJ, Koralek, DO, Rooney, I, Ribas, A, Larkin, J |
| المساهمون: | Larkin, James |
| سنة النشر: | 2017 |
| المجموعة: | The Institute of Cancer Research (ICR): Publications Repository |
| مصطلحات موضوعية: | Humans, Melanoma, Skin Neoplasms, Neoplasm Metastasis, Sulfonamides, Azetidines, Piperidines, Indoles, Proto-Oncogene Proteins B-raf, Antineoplastic Combined Chemotherapy Protocols, Neoplasm Staging, Prognosis, Survival Rate, Follow-Up Studies, Double-Blind Method, Mutation, Adult, Aged, 80 and over, Middle Aged, Female, Male, Young Adult, Biomarkers, Tumor, Vemurafenib |
| الوصف: | Background The combination of cobimetinib with vemurafenib improves progression-free survival compared with placebo and vemurafenib in previously untreated patients with BRAF(V600)-mutant advanced melanoma, as previously reported in the coBRIM study. In this Article, we report updated efficacy results, including overall survival and safety after longer follow-up, and selected biomarker correlative studies.Methods In this double-blind, randomised, placebo-controlled, multicentre study, adult patients (aged ≥18 years) with histologically confirmed BRAF(V600) mutation-positive unresectable stage IIIC or stage IV melanoma were randomly assigned (1:1) using an interactive response system to receive cobimetinib (60 mg once daily for 21 days followed by a 7-day rest period in each 28-day cycle) or placebo, in combination with oral vemurafenib (960 mg twice daily). Progression-free and overall survival were primary and secondary endpoints, respectively; all analyses were done on the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT01689519, and is ongoing but no longer recruiting participants.Findings Between Jan 8, 2013, and Jan 31, 2014, 495 eligible adult patients were enrolled and randomly assigned to the cobimetinib plus vemurafenib group (n=247) or placebo plus vemurafenib group (n=248). At a median follow-up of 14·2 months (IQR 8·5-17·3), the updated investigator-assessed median progression-free survival was 12·3 months (95% CI 9·5-13·4) for cobimetinib and vemurafenib versus 7·2 months (5·6-7·5) for placebo and vemurafenib (HR 0·58 [95% CI 0·46-0·72], p<0·0001). The final analysis for overall survival occurred when 255 (52%) patients had died (Aug 28, 2015). Median overall survival was 22·3 months (95% CI 20·3-not estimable) for cobimetinib and vemurafenib versus 17·4 months (95% CI 15·0-19·8) for placebo and vemurafenib (HR 0·70, 95% CI 0·55-0·90; p=0·005). The safety profile for cobimetinib and vemurafenib was tolerable and manageable, and no new safety signals were ... |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | Print-Electronic; 1260; application/pdf |
| اللغة: | English |
| تدمد: | 1470-2045 1474-5488 |
| العلاقة: | The Lancet. Oncology, 2016, 17 (9), pp. 1248 - 1260; https://repository.icr.ac.uk/handle/internal/664Test |
| DOI: | 10.1016/s1470-2045(16)30122-x |
| الإتاحة: | https://doi.org/10.1016/s1470-2045Test(16)30122-x https://repository.icr.ac.uk/handle/internal/664Test |
| حقوق: | https://www.rioxx.net/licenses/all-rights-reservedTest |
| رقم الانضمام: | edsbas.14F55AF0 |
| قاعدة البيانات: | BASE |
| تدمد: | 14702045 14745488 |
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| DOI: | 10.1016/s1470-2045(16)30122-x |