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Antitumor activity of ipilimumab or BRAF ± MEK inhibition after pembrolizumab in patients with advanced melanoma: analysis from KEYNOTE-006
Long, G. V. Arance, A. Mortier, L. Lorigan, Paul C Blank, C. Mohr, P. Schachter, J. Grob, J. J. Lotem, M. Middleton, M. R.
Long, G. V.
Arance, A.
Mortier, L.
Lorigan, Paul C
Blank, C.
Mohr, P.
Schachter, J.
Grob, J. J.
Lotem, M.
Middleton, M. R.
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Abstract
Background: 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.
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Date
2021
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Collections
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Article
Citation
Long 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.