PD-L1 status does not predict the outcome of BRAF inhibitor therapy in metastatic melanoma

Eur J Cancer. 2018 Jan;88:67-76. doi: 10.1016/j.ejca.2017.10.026. Epub 2017 Nov 28.

Abstract

Background: Targeted therapies with BRAF plus MEK inhibitors (BRAFi; MEKi) represent the major treatment strategy for patients with BRAF-mutated metastatic melanoma (MM). Previous analyses suggested a correlation between programmed death-ligand 1 (PD-L1) expression in tumour tissues and the outcome of targeted therapies. This study investigated PD-L1 as a potential predictive biomarker of BRAFi-based targeted therapies in MM patients.

Patients and methods: We analysed two independent cohorts of BRAF V600-mutated MM patients undergoing BRAFi-based therapies for PD-L1 expression in pre-treatment tumour tissues. The oligocentre cohort 1 included 83 patients whose tumour tissues were analysed retrospectively with the anti-PD-L1 antibody clone E1L3N. The multicentre cohort 2 included 58 patients whose tumour tissues were analysed prospectively within the framework of the "Registry of the Arbeitsgemeinschaft Dermatologische Onkologie" (ADOREG) and "Tissue Registry in Melanoma" (TRIM) project using the anti-PD-L1 antibody clone 28-8.

Results: PD-L1 expression in pre-treatment tumour tissue did not correlate with response or survival to BRAFi-based therapies in both MM patient cohorts. This finding was not influenced by retrospective versus prospective immunohistochemistry analyses, oligocentre versus multicentre cohorts or the different anti-PD-L1 antibody clones used. In cohort 1, PD-L1 positivity was detected in tumour tissue of 41.0% and 18.1% of patients (cut-off 1% and 5%, respectively). In cohort 2, 58.6% and 39.7% of patients showed PD-L1 positivity (cut-off 1% and 5%, respectively).

Conclusion: In two independent cohorts including a total of 141 MM patients, PD-L1 expression in tumour tissue did not correlate with the outcome of BRAFi-based treatment. Therefore, PD-L1 cannot be recommended for the use as a predictive biomarker of BRAFi-based therapy in BRAF V600-mutated MM.

Keywords: BRAF inhibitors; BRAF mutation; Biomarker; MEK inhibitors; Metastatic melanoma; PD-L1 expression.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • B7-H1 Antigen / biosynthesis*
  • Carbamates / administration & dosage
  • Carbamates / therapeutic use
  • Female
  • Humans
  • Imidazoles / administration & dosage
  • Imidazoles / therapeutic use
  • Indoles / administration & dosage
  • Indoles / therapeutic use
  • Kaplan-Meier Estimate
  • Male
  • Melanoma / drug therapy*
  • Melanoma / genetics
  • Melanoma / metabolism
  • Middle Aged
  • Mutation
  • Neoplasm Metastasis
  • Oximes / administration & dosage
  • Oximes / therapeutic use
  • Prognosis
  • Protein Kinase Inhibitors / therapeutic use*
  • Proto-Oncogene Proteins B-raf / antagonists & inhibitors*
  • Proto-Oncogene Proteins B-raf / genetics
  • Proto-Oncogene Proteins B-raf / metabolism
  • Retrospective Studies
  • Sulfonamides / administration & dosage
  • Sulfonamides / therapeutic use
  • Treatment Outcome
  • Vemurafenib
  • Young Adult

Substances

  • B7-H1 Antigen
  • CD274 protein, human
  • Carbamates
  • Imidazoles
  • Indoles
  • Oximes
  • Protein Kinase Inhibitors
  • Sulfonamides
  • Vemurafenib
  • encorafenib
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf
  • dabrafenib