Patients with metastatic melanoma treated with vemurafenib as monotherapy or in combination with cobimetinib.

Abstract

e21016 Background: This is a retrospective analysis of patients (pts) with metastatic melanoma (mM) designed to evaluate the efficacy and safety of vemurafenib as monotherapy (V) in comparison with vemurafenib in combination with cobimetinib (V+C) in routine clinical practice. Methods: Baseline characteristics, treatment-related adverse events, and efficacy data were collected from 58 mm pts who were treated with V and 32 mm pts treated with V+C. Cobimetinib was given within approved pre-approval access program. Results: In 39-month period, 241 pts were diagnosed with unresectable or mm and in 137 pts (57%) tumor tissue was positive for BRAF V600E/K mutation (89% BRAF V600E and 11% BRAF V600K). 58 BRAF-positive pts were treated with V (median age 55.1, 66% males, 62% pts with elevated LDH level, 74% M1c) and 32 BRAF-positive pts with V+C (median age 54.5, 69% males, 31% pts with elevated LDH level, 81% M1c). V was given as first, second or third line treatment to 49 (85%), 6 (10%) and 3 (5%) pts respectively, while V+C was given only as first line treatment. In pts with assessable disease (88% in V and 100% in V+C group) the overall response rate (ORR) was 41% in V group and 56% in V+C group. Disease control rate (DCR) was 69% in V group and 91% in V+C group. Complete responses (CR) were reported in 4 pts (7%) in V group and in 1 pts (3%) in V+C group. Partial responses (PR) were more frequent in V+C group (53%) than in V group (29%). Median progression-free survival (PFS) was 5.0 months (95% CI, 2.8-7.2) in V group and 7.9 months (95% CI, 6.1-9.7) in V+C group. Median overall survival (OS) was 6.7 months (95% CI, 4.0-9.4) in V group and 9.7 months (95% CI, 7.6-11.8) in V+C group. At the time of analysis 16% of pts are alive in V group and 41% in V+C group. The best outcomes had subgroup of pts with normal LDH level in V+C group (DCR = 95%), with 50% pts alive at the time of data analysis. Adverse events (AEs) were reported in 83% of pts in V group and 63% in V+C group and 83% and 94% of reported AEs were grade 1-2 respectively. Dose reduction was required in 50% of pts in V group and in 28% of pts in V+C group. Conclusions: Vemurafenib in combination with cobimetinib has shown meaningful efficacy and managable safety profile in real-world setting.