Biologic subtypes of melanoma predict survival benefit of combination anti-PD1+anti-CTLA4 immune checkpoint inhibitors versus anti-PD1 monotherapy
作者： Samuel D Saibil , April A N Rose , Marcus O Butler , Ian King , Zaid Saeed Kamil
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摘要: Purpose Anti-programmed cell death protein 1 (PD1)±anti-cytotoxic T-lymphocyte associated 4 (CTLA4) immune checkpoint inhibitors (ICIs) are standard therapeutic options for metastatic melanoma. We assessed whether biologic subtype according to primary tumor type or genomic can function as predictive biomarkers anti-PD1±anti-CTLA4 ICI in patients with advanced Methods performed a single-center retrospective cohort analysis of who received melanoma between 2012 and 2019. Primary type, BRAF NRAS mutation status, other covariates were abstracted from chart review. Log-rank tests multivariable Cox regression models used assess differences clinical progression-free (cPFS) overall survival (OS). Results identified 230 249 lines unresectable disease. Of these patients, 74% cutaneous, 11% mucosal, 8% unknown 7% acral. mutations 35% 28% respectively. In analyses the entire cohort, acral mucosal >3 sites, elevated LDH shorter cPFS OS. Combination therapy was longer (HR 0.57, 95% CI 0.38 0.86, p=0.007) OS 0.42, 0.28 0.65, p Conclusions our independent markers receiving anti-PD1 ICI. subtype—including NRAS—should be further evaluated prospective trials determine their value markers. Biologic subtypes may facilitate decision-making when recommending combination treatment (anti-PD1±anti-CTLA4) versus alone
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