Antitumor activity of ipilimumab or BRAF+/-MEK inhibition after pembrolizumab in patients with advanced melanoma in KEYNOTE-006

Abstract

In the KEYNOTE-006 (NCT01866319) study, pembrolizumab (10 mg/kg Q2W or Q3W) had superior OS vs ipilimumab (3 mg/kg, Q3W 4 doses) in patients with advanced melanoma who had <=1 prior therapy. At data cutoff (Dec 4, 2017) with a median follow-up of 46.9 months, of 555 patients treated with pembrolizumab, first subsequent therapy was ipilimumab in 103 patients; and BRAFi+/-MEKi in 59 patients (33 received BRAFi+MEKi, 26 received BRAFi alone). At the start of subsequent ipilimumab therapy, 73.8% had ECOG PS of 0 or 1; 35.0% had elevated LDH. At the start of subsequent BRAFi+/-MEKi therapy, 76.3% had ECOG PS of 0 or 1; 35.6% had elevated LDH; 37% had received BRAFi+/-MEKi before study enrollment. In the subsequent ipilimumab group, ORR with pembrolizumab was 17.5% (1 CR; 17 PR); median ipilimumab treatment duration was 1.7 months (range, 1 day-6.9 months); ORR with ipilimumab was 15.5%; 11 (8 CR, 3 PR) of 16 responses were ongoing; median OS from ipilimumab start was 9.8 months (95% CI, 7.7-16.4). In the BRAFi+/-MEKi group, ORR with pembrolizumab was 13.5% (8 PR); median BRAFi+/-MEKi duration was 7.2 months (range, 0.4-44.4); ORR with BRAFi+/-MEKi was 30.5%; 7 (4 CR, 3 PR) of 18 responses were ongoing; median OS from BRAFi+/-MEKi start was 12.9 months (95% CI, 9.9-20.8). Of 22 patients in the BRAFi+/-MEKi group who received prior BRAFi+/-MEKi, ORR was 9.1%; 1 responder (CR) had ongoing response. Of 37 patients in the BRAFi+/-MEKi group who received no prior BRAFi+/-MEKi, ORR was 43.2%; 6 responders (3 CR) had ongoing response. In conclusion, ipilimumab and BRAFi+/-MEKi both have antitumor activity as the first subsequent therapy after pembrolizumab in patients with advanced melanoma.