Abstract
BackgroundAnti-PD-1 and BRAF-inhibitors (BRAFi) have been approved as first-line treatments in advanced melanoma. To date, no prospective data are available to give the best sequence of treatment. The objective of this study was to evaluate in real-life the efficacy of anti-PD-1 after BRAFi, ipilimumab, or chemotherapy failure.MethodsThis was a single institution cohort analysis in patients treated with anti-PD-1 right after BRAFi, ipilimumab, or chemotherapy failure. Melanoma evolution after anti-PD-1 initiation was analyzed in BRAF-mutated and BRAF wild-type patients. The efficacy of treatment was evaluated by Objective Response Rate (ORR), Disease Control Rate (DCR), Progression-Free Survival (PFS), and Overall Survival (OS).ResultsSeventy-four patients were included: 33 wild-type and 41 BRAF-mutated melanoma. ORR to anti-PD-1 was significantly lower in BRAF-mutated patients (12.2% vs. 45.5%, p = 0.002). After anti-PD-1 initiation, the median PFS and OS was significantly shorter in the BRAF mutated group (2 vs. 5 months and 7 vs. 20 months, p = 0.001). The hazard ratio for disease progression was of 2.3 (95%CI:1.3–3.9; p = 0.003) and 2.5 (95%CI:1.3–4.5; p = 0.005) for death. Thirty-nine percent of BRAF-mutated-patients died within 3 months after anti-PD-1 initiation. Rapid death (≤3 months) was significantly higher in BRAF-mutated patients (55.2% vs. 20.0%, p = 0.014).DiscussionThis is the largest series of unselected patients treated in real-life with anti-PD-1 as second-or-higher line of treatment. Anti-PD-1 was less effective in BRAF-mutated cases as a majority of patients presented aggressive tumor evolution after BRAFi discontinuation. These data are consistent with previous studies suggesting a negative impact of BRAFi prior to immunotherapy.
Highlights
Anti-Programmed Death-1 (PD-1) and BRAF-inhibitors (BRAFi) have been approved as first-line treatments in advanced melanoma
BRAFi alone was used in 15 patients (36.6%), and BRAFi combined with MEK inhibitor (MEKi) in and 26 patients (63.4%; Table 1)
We report here the largest retrospective series of unselected patients treated in real-life during the period when anti-PD-1 was only allowed in patients previously treated by anti Cytotoxic Tlymphocyte–associated antigen-4 (CTLA-4) or BRAFi according to BRAF status
Summary
Anti-PD-1 and BRAF-inhibitors (BRAFi) have been approved as first-line treatments in advanced melanoma. The objective of this study was to evaluate in real-life the efficacy of anti-PD-1 after BRAFi, ipilimumab, or chemotherapy failure. Tyrosine kinase inhibitors and checkpoint inhibitor immunotherapies including anti CTLA-4 and anti PD-1 monoclonal antibodies have markedly improved prognosis of advanced melanoma [1]. In 2013, the society for immunotherapy published consensus recommendations for the use of immunotherapy in the management of advanced melanoma in the USA [2]. Amini-Adle et al BMC Cancer (2018) 18:705 efficacy of anti-PD-1 after BRAFi failure in real-life conditions of use. The objective of this study was to evaluate and compare the efficacy of anti-PD-1 in real-life use after progression during BRAFi or anti-CTLA-4 or chemotherapy in metastatic melanoma patients
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