Cobimetinib combined with vemurafenib improves survival outcomes

June 7, 2018


Background: The coBRIM study demonstrated that first-line C+V improved progression-free (PFS) and overall survival (OS) compared with placebo (P)+V in pts with BRAFV600-mutated advanced melanoma. We report updated survival outcomes and safety after extended follow-up. 

Methods: coBRIM was a double-blind, multicenter study in which 495 patients were randomized to receive C (60 mg once daily for 21 days followed by a 7-day rest period in each 28-day cycle; n = 247) or P (n = 248) in combination with V (960 mg twice daily). PFS and OS were primary and secondary endpoints, respectively. 

Results: At database closure, median follow-up duration for the overall intent-to-treat population was 18.6 months (range, 0.5–55.1 months); 176 pts (71%) in the C+V arm and 190 pts (77%) in the P+V arm had discontinued the study, with the most common reason being death (C+V = 148 pts [60%]; P+V = 162 pts [65%]). Median PFS among pts receiving C+V was 12.6 months (95% confidence interval [CI], 9.5–14.7 months) vs 7.2 months (95% CI, 5.6–7.5 months) in pts receiving P+V. Median OS among pts receiving C+V was 22.5 months (95% CI, 20.3–28.8 months) vs 17.4 months (95% CI, 15.2–20.5 months) in pts receiving P+V. A greater proportion of pts receiving C+V were alive at 1, 2, 3 and 4 years vs pts receiving P+V (Table). Median duration of treatment in the C+V arm was 9.0 months (range, 0.1–53.1 months) for C and 9.2 months (range, 0.3–53.3 months) for V. Pts in the P+V arm had a shorter median duration of treatment of 5.6 months (range, 0.2–43.9 months) for P and 5.7 months (0.2–53.2 months) for V. Grade 3/4 adverse events (AEs) were reported in 75% and 61% of pts in the C+V and P+V arms, respectively. Grade 5 AEs were reported in 2% of pts in each study arm. A larger proportion of pts discontinued C+V (19%) versus P+V (10%) due to AEs. 

Conclusions: Extended follow-up of the phase 3 coBRIM study confirmed the survival benefit of C+V over P+V. No new safety signals were observed. Clinical trial information: NCT01689519.


Efficacy and safety of cobimetinib (C) combined with vemurafenib (V) in patients (pts) with BRAFV600 mutation–positive metastatic melanoma: analysis from the 4-year extended follow-up of the phase 3 coBRIM study. Brigitte Dreno Journal of Clinical Oncology 2018 36:15_suppl, 9522-9522, (May 20 2018), DOI: 10.1200/JCO.2018.36.15

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