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Antitumor activity of ipilimumab or BRAF +/- MEK inhibition after pembrolizumab treatment in patients with advanced melanoma: analysis from KEYNOTE-006
Journal Contribution - Journal Article
Background: Antitumor activity of ipilimumab or BRAF +/- MEK inhibitors (BRAFi +/- MEKi) following pembrolizumab administration in melanoma is poorly characterized.
Patients and methods: In the phase III KEYNOTE-006 study, patients with unresectable stage III/IV melanoma received pembrolizumab (10 mg/kg) once every 2 or 3 weeks (Q3W) or ipilimumab (3 mg/kg) Q3W. The current post hoc analysis evaluates outcomes with ipilimumab or BRAFi +/- MEKi as first subsequent systemic therapy after pembrolizumab administration and includes patients who completed or discontinued pembrolizumab after one or more dose. Pembrolizumab arms were pooled.
Results: At data cut-off (4 December 2017), median follow-up was 46.9 months. Of 555 pembrolizumab-treated patients, first subsequent therapy was ipilimumab for 103 (18.6%) and BRAFi +/- MEKi for 59 (10.6%) [33 received BRAFi thorn MEKi, 26 BRAFi alone; 37 (62.7%) were BRAFi +/- MEKi naive]. In the subsequent ipilimumab group, ORR with previous pembrolizumab was 17.5% [1 complete response (CR); 17 partial response (PR)]; 79.6% had discontinued pembrolizumab due to progressive disease (PD); median overall survival (OS) was 21.5 months. ORR with subsequent ipilimumab was 15.5%; 11/16 responses (8 CRs; 3 PRs) were ongoing. ORR with subsequent ipilimumab was 9.7% for patients with PD as best response to pembrolizumab. Median OS from ipilimumab initiation was 9.8 months. In the subsequent BRAFi +/- MEKi group, ORR with previous pembrolizumab was 13.5% (8 PR); 76.3% had discontinued pembrolizumab due to PD; median OS was 17.9 months. ORR with subsequent BRAFi +/- MEKi was 30.5%, 7/18 responses (4 CR, 3 PR) were ongoing. Median OS from BRAFi +/- MEKi initiation was 12.9 months. ORR for BRAFi +/- MEKi-naive patients who received subsequent BRAFi +/- MEKi was 43.2%; 6/16 were ongoing (3 CR, 3 PR).
Conclusions: Ipilimumab and BRAFi +/- MEKi have antitumor activity as first subsequent therapy after pembrolizumab in patients with advanced melanoma.
Patients and methods: In the phase III KEYNOTE-006 study, patients with unresectable stage III/IV melanoma received pembrolizumab (10 mg/kg) once every 2 or 3 weeks (Q3W) or ipilimumab (3 mg/kg) Q3W. The current post hoc analysis evaluates outcomes with ipilimumab or BRAFi +/- MEKi as first subsequent systemic therapy after pembrolizumab administration and includes patients who completed or discontinued pembrolizumab after one or more dose. Pembrolizumab arms were pooled.
Results: At data cut-off (4 December 2017), median follow-up was 46.9 months. Of 555 pembrolizumab-treated patients, first subsequent therapy was ipilimumab for 103 (18.6%) and BRAFi +/- MEKi for 59 (10.6%) [33 received BRAFi thorn MEKi, 26 BRAFi alone; 37 (62.7%) were BRAFi +/- MEKi naive]. In the subsequent ipilimumab group, ORR with previous pembrolizumab was 17.5% [1 complete response (CR); 17 partial response (PR)]; 79.6% had discontinued pembrolizumab due to progressive disease (PD); median overall survival (OS) was 21.5 months. ORR with subsequent ipilimumab was 15.5%; 11/16 responses (8 CRs; 3 PRs) were ongoing. ORR with subsequent ipilimumab was 9.7% for patients with PD as best response to pembrolizumab. Median OS from ipilimumab initiation was 9.8 months. In the subsequent BRAFi +/- MEKi group, ORR with previous pembrolizumab was 13.5% (8 PR); 76.3% had discontinued pembrolizumab due to PD; median OS was 17.9 months. ORR with subsequent BRAFi +/- MEKi was 30.5%, 7/18 responses (4 CR, 3 PR) were ongoing. Median OS from BRAFi +/- MEKi initiation was 12.9 months. ORR for BRAFi +/- MEKi-naive patients who received subsequent BRAFi +/- MEKi was 43.2%; 6/16 were ongoing (3 CR, 3 PR).
Conclusions: Ipilimumab and BRAFi +/- MEKi have antitumor activity as first subsequent therapy after pembrolizumab in patients with advanced melanoma.
Journal: Annals Oncol 2002
ISSN: 0923-7534
Issue: 2
Volume: 33
Pages: 204-215
Publication year:2022
Keywords:advanced melanoma, pembrolizumab, ipilimumab, BRAF inhibition, MEK inhibition
Accessibility:Open