Ineffective anti PD-1 therapy after BRAF inhibitor failure in advanced melanoma

• Published in: BMC cancer Vol. 18; no. 1; p. 705
• Main Authors: Amini-Adle, M, Khanafer, N, Le-Bouar, M, Duru, G, Dalle, S, Thomas, L
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 03.07.2018; BioMed Central; BMC
• Subjects: Adult; Aged; Anti PD-1; Bacteriology; BRAF inhibitor; Cancer therapies; Care and treatment; Female; Health aspects; Humans; Immunology; Immunotherapy; Ipilimumab - therapeutic use; Life Sciences; Lymphatic system; Male; Medical prognosis; Melanoma; Melanoma - drug therapy; Melanoma - genetics; Melanoma - mortality; Metastasis; Microbiology and Parasitology; Middle Aged; Monoclonal antibodies; Mutation; PD-1 protein; Prognosis; Programmed Cell Death 1 Receptor - antagonists & inhibitors; Proto-Oncogene Proteins B-raf - antagonists & inhibitors; Proto-Oncogene Proteins B-raf - genetics; Retrospective Studies; Targeted cancer therapy; Treatment Failure; Treatment sequence; Tyrosine; Vemurafenib; Virology; BRAF inhibitor; Treatment sequence; Immunotherapy; Melanoma; Anti PD-1
• ISSN: 1471-2407; 1471-2407
• DOI: 10.1186/s12885-018-4618-9

Anti-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. This 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). Seventy-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). This 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.