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

Autor: Stéphane Dalle, Gérard Duru, Luc Thomas, Mona Amini-Adle, M. Le-Bouar, N. Khanafer
Přispěvatelé: Département de Dermatologie [CH Lyon-Sud, Pierre-Bénite], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Laboratoire des pathogènes émergents -- Emerging Pathogens Laboratory (LPE-Fondation Mérieux), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Biostatistique des Hospices Civils de Lyon, Hospices Civils de Lyon (HCL), Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)
Jazyk: angličtina
Rok vydání: 2018
Předmět:
0301 basic medicine
Oncology
Male
Cancer Research
medicine.medical_treatment
Programmed Cell Death 1 Receptor
0302 clinical medicine
Surgical oncology
Treatment Failure
Melanoma
Hazard ratio
Middle Aged
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
3. Good health
030220 oncology & carcinogenesis
[SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology
[SDV.IMM]Life Sciences [q-bio]/Immunology
Female
Immunotherapy
medicine.drug
Cohort study
Research Article
Adult
Proto-Oncogene Proteins B-raf
BRAF inhibitor
medicine.medical_specialty
Treatment sequence
Ipilimumab
lcsh:RC254-282
03 medical and health sciences
Internal medicine
Genetics
medicine
Humans
neoplasms
Aged
Retrospective Studies
Chemotherapy
business.industry
medicine.disease
[SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology
Discontinuation
Anti PD-1
030104 developmental biology
Mutation
business
Zdroj: BMC Cancer
BMC Cancer, 2018, 18 (1), pp.705. ⟨10.1186/s12885-018-4618-9⟩
BMC Cancer, Vol 18, Iss 1, Pp 1-7 (2018)
BMC Cancer, BioMed Central, 2018, 18 (1), pp.705. ⟨10.1186/s12885-018-4618-9⟩
ISSN: 1471-2407
DOI: 10.1186/s12885-018-4618-9⟩
Popis: International audience; BACKGROUND: 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. METHODS: 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). RESULTS: 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 (
Databáze: OpenAIRE
Externí odkaz: