Abstract
BackgroundPrescribing 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.MethodsThis 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.ResultsBetter 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).ConclusionsCombining these reproducible biomarkers could help improve therapeutic decision-making for patients with progressive disease.
Highlights
Melanomas are highly immunogenic cancers,[1] whose prognoses have been dramatically improved by immunotherapy
Pembrolizumab was given to 72.9% of the patients and nivolumab to 27.1%
The 6-month Overall response rates (ORRs) was 28.6%, with 69.7% (57.42–79.09%) overall survival (OS), median progression-free survival (PFS) lasted 5.75 (2.99–10.28) months, and median OS 15.9 months
Summary
Melanomas are highly immunogenic cancers,[1] whose prognoses have been dramatically improved by immunotherapy. Tumour-cell programmed death-ligand-1 (PD-L1) expression has been associated with better outcomes under anti-PD-1 immunotherapy: a recent meta-analysis highlighted better odds ratios of ORRs for the 1%- and 5%-positive tumour-cell thresholds (respectively, 2.81, P = 0.0002; and 2.22, P < 0.00001).[8] because all studies reported significant response rates of PD-L1– melanomas,[9] PD-L1–status determination is not mandatory for the prescription of these agents to melanoma patients, unlike lung adenocarcinomas.[10]. RESULTS: 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). CONCLUSIONS: Combining these reproducible biomarkers could help improve therapeutic decision-making for patients with progressive disease
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