Antitumor activity of ipilimumab or BRAF ± MEK inhibition after pembrolizumab treatment in patients with advanced melanoma: analysis from KEYNOTE-006.
Ann Oncol
; 33(2): 204-215, 2022 02.
Article
in En
| MEDLINE
| ID: mdl-34710571
ABSTRACT
BACKGROUND:
Antitumor activity of ipilimumab or BRAF ± MEK inhibitors (BRAFi ± MEKi) following pembrolizumab administration in melanoma is poorly characterized. PATIENTS ANDMETHODS:
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 + 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 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-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.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Proto-Oncogene Proteins B-raf
/
Melanoma
Limits:
Humans
Language:
En
Journal:
Ann Oncol
Year:
2022
Document type:
Article