PD-L1 Tumor Expression as a Predictive Biomarker of Immune Checkpoint Inhibitors’ Response and Survival in Advanced Melanoma Patients in Brazil

Author:

Sorroche Bruna Pereira1ORCID,Teixeira Renan de Jesus1,Pereira Caio Augusto Dantas2,Santana Iara Viana Vidigal3,Vujanovic Lazar45ORCID,Vazquez Vinicius de Lima16,Arantes Lidia Maria Rebolho Batista1ORCID

Affiliation:

1. Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos 14784-400, Brazil

2. Department of Clinical Oncology, Barretos Cancer Hospital, Barretos 14784-400, Brazil

3. Department of Pathology, Barretos Cancer Hospital, Barretos 14784-400, Brazil

4. UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA 15260, USA

5. Department of Otolaryngology, University of Pittsburgh, Pittsburgh, PA 15260, USA

6. Melanoma, Sarcoma, and Mesenchymal Tumors Surgery Department, Barretos Cancer Hospital, Barretos 14784-400, Brazil

Abstract

Immune checkpoint blockade (ICB) agents are prominent immunotherapies for the treatment of advanced melanoma. However, they fail to promote any durable clinical benefit in a large cohort of patients. This study assessed clinical and molecular predictors of ICB response and survival in advanced melanoma. A retrospective analysis was performed on 210 patients treated with PD-1 or CTLA-4 inhibitors at Barretos Cancer Hospital, Brazil. PD-L1 expression was assessed by immunohistochemistry using formalin-fixed paraffin-embedded tumor tissues collected prior to ICB therapy. Patients were divided into responders (complete and partial response and stable disease for more than 6 months) and non-responders (stable disease for less than 6 months and progressive disease). Among them, about 82% underwent anti-PD-1 immunotherapy, and 60.5% progressed after the ICB treatment. Patients that received ICB as first-line therapy showed higher response rates than previously treated patients. Higher response rates were further associated with superficial spreading melanomas and positive PD-L1 expression (>1%). Likewise, PD-L1 positive expression and BRAF V600 mutations were associated with a higher overall survival after ICB therapy. Since ICBs are expensive therapies, evaluation of PD-L1 tumor expression in melanoma patients should be routinely assessed to select patients that are most likely to respond.

Funder

Fundação de Amparo à Pesquisa do Estado de São Paulo

National Council for Scientific and Technological Development

Publisher

MDPI AG

Subject

Clinical Biochemistry

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