Clinical predictors of response for coBRIM: A phase III study of cobimetinib (C) in combination with vemurafenib (V) in advanced BRAF-mutated melanoma (MM).
2016; Lippincott Williams & Wilkins; Volume: 34; Issue: 15_suppl Linguagem: Inglês
10.1200/jco.2016.34.15_suppl.9528
ISSN1527-7755
AutoresJames Larkin, Grant A. McArthur, Antoni Ribas, Paolo A. Ascierto, Jorge D. Gallo, Isabelle Rooney, Ilsung Chang, Brigitte Dréno,
Tópico(s)Protein Degradation and Inhibitors
Resumo9528 Background: The coBRIM study showed significant improvement in overall survival (OS), progression-free survival (PFS), and overall response rate (ORR) in patients (pts) with BRAFV600 mutation–positive mm treated with V+C, compared with V alone. Herein we report an exploratory analysis of baseline characteristics (BLCs) that may help predict complete response (CR) and the impact of CR and dose modification (DM) on OS and PFS. Methods: Study methods were previously described (Larkin J et al. N Engl J Med 2014;371:1867-1876.). Kaplan-Meier curves for OS and PFS by tumor response (RECIST v1.1) were performed. Tumor responses were tabulated by BLC. Results: A total of 247 pts were randomly assigned to receive C+V and 248 pts to receive P+V. PFS and OS favored the C+V arm, with hazard ratio (HR) of 0.58 (P< 0.0001) and 0.70 (P= 0.005), respectively. ORR (data cutoff Jan 16, 2015) was 70% (16% CR) in the C+V arm vs 50% (10% CR) in the P+V arm. Pts treated with C+V generally have a higher ORR and CR across BLCs than pts on P+V (Table). Pts with normal and high LDH levels treated with C+V had higher CR rates than those treated with P+V. Median PFS for pts on C+V who attained CR was 19.8 mo and for pts with partial response (PR) (70%) was 13.3 mo. In contrast, pts on C+V who had either stable disease (SD) or progressive disease (PD) (30%) as best response achieved median PFS of 3.9 mo and 1.9 mo, respectively. Similar trends were observed for OS. DM (dose reduction or temporary interruption of 1 or both drugs) did not seem to affect efficacy outcomes. Pts in the C+V arm with DM of both drugs achieved median PFS comparable with the median PFS of pts without DM. Conclusions: C+V resulted in high ORR and CR rates. In the C+V arm, high response rates were apparent across the assessed BLCs, but higher rates of CR are achieved in pts with certain BLCs. Better response (PR, CR) was associated with improved PFS and OS in the C+V arm. DM of 1 or both drugs did not seem to affect efficacy of the combination. Clinical trial information: NCT01689519.BLC P+V C+V CR, % PR, % CR, % PR, % Age < 65 11 43 13 61 Age ≥65 11 33 28 43 Sex F 13 42 23 58 Sex M 9 39 13 56 Stg IIIC-M1b 22 45 26 50 Stg M1c 4 38 11 61 ECOG PS 0 15 39 18 57 ECOG PS 1 3 44 14 55 LDH normal 16 48 23 56 LDH high 4 32 9 57 V600E 11 43 14 58 V600K 7 34 23 55
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