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Ref Type Journal Article
PMID (29973670)
Authors Dupuis F, Lamant L, Gerard E, Torossian N, Chaltiel L, Filleron T, Beylot-Barry M, Dutriaux C, Prey S, Gros A, Jullie ML, Meyer N, Vergier B
Title Clinical, histological and molecular predictors of metastatic melanoma responses to anti-PD-1 immunotherapy.
Journal Vol Issue Date Pages Journal Short Title
British journal of cancer 119 2 2018 Jul 193-199 Br J Cancer
URL
Abstract Text Prescribing anti-programmed death-1 (PD-1) immunotherapy for advanced melanoma is currently not restricted by any biomarker assessment. Determination of programmed death-ligand-1 (PD-L1)-expression status is technically challenging and is not mandatory, because negative tumours also achieve therapeutic responses. However, reproducible biomarkers predictive of a response to anti-PD-1 therapy could contribute to improving therapeutic decision-making.This retrospective study on 70 metastatic melanoma patients was undertaken to evaluate the relationships between clinical, histological, immunohistochemical and/or molecular criteria, and the 6-month objective response rate.Better objective response rates were associated with metachronous metastases (P = 0.04), PD-L1 tumour- and/or immune-cell status (P = 0.01), CD163+ histiocytes at advancing edges (P = 0.009) of primary melanomas and NRAS mutation (P = 0.019). Moreover, CD163+ histiocytes at advancing edges (P = 0.04) were associated with longer progression-free survival (PFS), and metachronous metastases with longer overall survival (P = 0.02) and PFS (P = 0.049).Combining these reproducible biomarkers could help improve therapeutic decision-making for patients with progressive disease.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
CD274 positive melanoma predicted - sensitive Nivolumab Clinical Study - Cohort Actionable In a clinical study, PD-L1 (CD274) expression in primary melanomas, but not the PD-L1 status of advancing edges or metastases, was associated with higher 6-month objective response rate (35.7% in PD-L1 positive vs. 5% in PD-L1 negative; p=0.02) following treatment with Keytruda (pembrolizumab) or Opdivo (nivolumab) in patients with metastatic melanoma (PMID: 29973670). 29973670
NRAS mutant melanoma predicted - sensitive Pembrolizumab Clinical Study - Cohort Actionable In a clinical study, NRAS mutations were associated with higher 6-month objective response rate (53.3% vs. 19.6% without NRAS mutations; p=0.019) following treatment with Keytruda (pembrolizumab) or Opdivo (nivolumab) in patients with metastatic melanoma, however, progression-free survival and overall survival were similar between patients with and without NRAS mutations (PMID: 29973670). 29973670
CD274 positive melanoma predicted - sensitive Pembrolizumab Clinical Study - Cohort Actionable In a clinical study, PD-L1 (CD274) expression in primary melanomas, but not the PD-L1 status of advancing edges or metastases, was associated with higher 6-month objective response rate (35.7% in PD-L1 positive vs. 5% in PD-L1 negative; p=0.02) following treatment with Keytruda (pembrolizumab) or Opdivo (nivolumab) in patients with metastatic melanoma (PMID: 29973670). 29973670
NRAS mutant melanoma predicted - sensitive Nivolumab Clinical Study - Cohort Actionable In a clinical study, NRAS mutations were associated with higher 6-month objective response rate (53.3% vs. 19.6% without NRAS mutations; p=0.019) following treatment with Keytruda (pembrolizumab) or Opdivo (nivolumab) in patients with metastatic melanoma, however, progression-free survival and overall survival were similar between patients with and without NRAS mutations (PMID: 29973670). 29973670