5-Year Outcomes with Cobimetinib plus Vemurafenib in BRAFV600 Mutation-Positive Advanced Melanoma: Extended Follow-up of the coBRIM Study

Ascierto, PA; Dreno, B; Larkin, J; Ribas, A; Liszkay, G; Maio, M; Mandala, M; Demidov, L; Stroyakovskiy, D; Thomas, L; de la Cruz-Merino, L; Atkinson, V; Dutriaux, C; Garbe, C; Hsu, J; Jones, S; Li, H; McKenna, E; Voulgari, A; McArthur, GA

Author(s): Ascierto, PA; Dreno, B; Larkin, J; Ribas, A; Liszkay, G; Maio, M; Mandala, M; Demidov, L; Stroyakovskiy, D; Thomas, L; de la Cruz-Merino, L; Atkinson, V; Dutriaux, C; Garbe, C; Hsu, J; Jones, S; Li, H; McKenna, E; Voulgari, A; McArthur, GA;
Details: Publication Year 2021-10,Volume 27,Issue #19,Page 5225-5235
Journal Title: Clinical Cancer Research
Publication Type: Research article
Abstract: PURPOSE: The randomized phase III coBRIM study (NCT01689519) demonstrated improved progression-free survival (PFS) and overall survival (OS) with addition of cobimetinib to vemurafenib compared with vemurafenib in patients with previously untreated BRAFV600 mutation-positive advanced melanoma. We report long-term follow-up of coBRIM, with at least 5 years since the last patient was randomized. PATIENTS AND METHODS: Eligible patients were randomized 1:1 to receive either oral cobimetinib (60 mg once daily on days 1-21 in each 28-day cycle) or placebo in combination with oral vemurafenib (960 mg twice daily). RESULTS: 495 patients were randomized to cobimetinib plus vemurafenib (n = 247) or placebo plus vemurafenib (n = 248). Median follow-up was 21.2 months for cobimetinib plus vemurafenib and 16.6 months for placebo plus vemurafenib. Median OS was 22.5 months (95% CI, 20.3-28.8) with cobimetinib plus vemurafenib and 17.4 months (95% CI, 15.0-19.8) with placebo plus vemurafenib; 5-year OS rates were 31% and 26%, respectively. Median PFS was 12.6 months (95% CI, 9.5-14.8) with cobimetinib plus vemurafenib and 7.2 months (95% CI, 5.6-7.5) with placebo plus vemurafenib; 5-year PFS rates were 14% and 10%, respectively. OS and PFS were longest in patients with normal baseline lactate dehydrogenase levels and low tumor burden, and in those achieving complete response. The safety profile remained consistent with previously published reports. CONCLUSIONS: Extended follow-up of coBRIM confirms the long-term clinical benefit and safety profile of cobimetinib plus vemurafenib compared with vemurafenib monotherapy in patients with BRAFV600 mutation-positive advanced melanoma.
Keywords: Antineoplastic Combined Chemotherapy Protocols/adverse effects; Azetidines; Follow-Up Studies; Humans; *Melanoma/drug therapy/genetics; Mutation; Piperidines; Proto-Oncogene Proteins B-raf/genetics; *Skin Neoplasms/pathology; Vemurafenib/adverse effects
Department(s): Medical Oncology; Laboratory Research
PubMed ID: 34158360
Publisher's Version: https://doi.org/10.1158/1078-0432.CCR-21-0809
Open Access at Publisher's Site: https://doi.org/10.1158/1078-0432.CCR-21-0809
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2025-05-23 08:13:54

Last Modified: 2025-05-23 08:15:07