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

G. V. Long, A. Arance, L. Mortier, P. Lorigan, C. Blank, P. Mohr, J. Schachter, J. -J. Grob, M. Lotem, M. R. Middleton, B. Neyns, N. Steven, A. Ribas, E. Walpole, M. S. Carlino, C. Lebbe, M. Sznol, E. Jensen, M. A. Leiby, N. IbrahimC. Robert

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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.
Originele taal-2English
Pagina's (van-tot)204-215
Aantal pagina's12
TijdschriftAnnals of Oncology
Nummer van het tijdschrift2
StatusPublished - feb 2022

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