Antitumor activity of ipilimumab or BRAF ± MEK inhibition after pembrolizumab in patients with advanced melanoma: analysis from KEYNOTE-006
AuthorsLong, G. V.
Lorigan, Paul C
Grob, J. J.
Middleton, M. R.
Carlino, M. S.
Leiby, M. A.
AffiliationMelanoma Institute Australia, the University of Sydney, Mater Hospital, and Royal North Shore Hospital, Sydney, NSW, Australia
MetadataShow full item record
AbstractBackground: Antitumor activity of ipilimumab or BRAF ± MEK inhibition (BRAFi ± MEKi) following pembrolizumab in melanoma is poorly characterized. Patients and methods: In the phase 3 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 and includes patients who completed or discontinued pembrolizumab after ≥1 dose. Pembrolizumab arms were pooled. Results: At data cutoff (December 4, 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 + MEKi, 26 BRAFi alone; 37 [62.7%] were BRAFi ± MEKi-naïve). 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 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-naïve 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.
CitationLong GV, Arance A, Mortier L, Lorigan P, Blank C, Mohr P, et al. Antitumor activity of ipilimumab or BRAF ± MEK inhibition after pembrolizumab treatment in patients with advanced melanoma: analysis from KEYNOTE-006 [Internet]. Annals of Oncology. Elsevier BV; 2021.
JournalAnnals of Oncology
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