Objective responses can be obtained by CTLA-4 inhibition in metastatic melanoma after BRAF inhibitor failure.
The aim of this study was to determine the activity of ipilimumab (ipi)-based therapy after treatment failure with a BRAF inhibitor (BRAFi). Sixty-four patients with unresectable stage III or stage IV BRAF V600-mutant melanoma who were treated sequentially with a BRAFi and ipi-based therapy [ipi as monotherapy or ipi in combination with an autologous mRNA electroporated dendritic cell vaccine (TriMixDC-MEL)] were identified. Thirty-three patients had been treated with a BRAFi before ipi-based therapy (BRAFi-first), and 31 patients had been treated with ipi-based therapy first (ipi-first). In patients treated with a BRAFi first (n=33), the best response on sequential ipi-based therapy was three complete responses and six partial responses (best objective response rate of 27%). In patients treated with ipi-based therapy first (n=31), the best response on ipi-based therapy was 0 complete response and four partial responses (best objective response rate of 13%). The response rate did not differ significantly between the two groups (P=0.14). The median overall survival from the start of ipi-based therapy was 10 months (95% confidence interval: 5.7-14.3) in the BRAFi-first group and 12.3 months (95% confidence interval: 7.4-17.2) in the ipi-first group (P=0.34). We report that objective tumor responses to ipi-based immunotherapy can still be obtained after progression has occurred upon treatment with a BRAFi. A part of this observation might be related to the results obtained with a combination of ipi and TriMixDC-MEL.
aDepartment of Medical Oncology, UZ Brussels bDepartment of Dermatology, Hospital Erasme, Brussels cDepartment of Dermatology, UZ Gent, Ghent, Belgium.
Max S
MS
Schreuer
Ines L
IL
Chevolet
Yanina J
YJ
Jansen
Teofila C
TC
Seremet
Sofie
S
Wilgenhof
Danielle
D
Liénard
Veronique
V
Del Marmol
Bart
B
Neyns
D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D015415:Biomarkers / Q000378:metabolism; D060908:CTLA-4 Antigen / Q000378:metabolism*; D019496:Cancer Vaccines / Q000627:therapeutic use; D018450:Disease Progression; D018274:Electroporation; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D000074324:Ipilimumab; D008545:Melanoma / Q000188:drug therapy* / Q000378:metabolism; D009362:Neoplasm Metastasis; D011237:Predictive Value of Tests; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors*; D012333:RNA, Messenger / Q000378:metabolism; D012189:Retrospective Studies; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D015415:Biomarkers; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D019496:Cancer Vaccines; D000074324:Ipilimumab; D012333:RNA, Messenger; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf