Immune checkpoint inhibitors (ICIs) improve survival outcomes in metastatic melanoma and non-small cell lung cancer (NSCLC).,Preclinical evidence suggests that overexpression of cyclo-oxygenase-2 (COX2) in tumors facilitates immune evasion through prostaglandin E2 production and that COX inhibition synergizes with ICIs to promote antitumor T-cell activation.,This study investigates whether concurrent COX inhibitor (COXi) use during ICI treatment compared with ICI alone is associated with improved time-to-progression (TTP), objective response rate (ORR) and overall survival (OS) in patients with metastatic melanoma and NSCLC.,We retrospectively reviewed 90 metastatic melanoma and 37 metastatic NSCLC patients, treated with ICI between 2011 and 2019.,Differences in TTP and OS by ICI+COXi versus ICI alone were compared using Kaplan-Meier and Cox regression.,Interaction between ICI+COXi versus ICI alone and pretreatment neutrophil-lymphocyte ratio (NLR) was examined.,Independent radiology review per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 was performed.,For patients with melanoma, median TTP was significantly prolonged in ICI+COXi versus ICI alone (245 vs 100.5 days, p=0.002).,On multivariate analysis, ICI+COXi associated with increased TTP (HR 0.36, 95% CI 0.2 to 0.66, p=0.001), adjusted for age, pretreatment NLR, and gender.,For NSCLC patients, ICI+COXi also associated with increased TTP compared with ICI alone on multivariate analysis (HR 0.45; 95% CI 0.21 to 0.97; p=0.042) adjusted for age.,ORR at 6 months was significantly higher in patients who received ICI+COXi compared with ICI alone in both melanoma (58.6% vs 19.2%, p=0.0005) and NSCLC (73.7% vs 33.3%, p=0.036) cohorts.,In the melanoma cohort, high pretreatment NLR (>5) associated with decreased TTP (HR 3.21, 95% CI 1.64 to 6.3; p=0.0007); however, ICI+COXi significantly associated with increased TTP in high NLR (>5) patients (HR 0.08, 95% CI 0.03 to 0.25), but not in low NLR (≤5) patients (HR 0.65, 95% CI 0.32 to 1.32).,Similar outcomes were found in an adjusted melanoma cohort after RECIST review.,Our study suggests that COXi use concurrently with ICI significantly associated with longer TTP and improved ORR at 6 months in patients with metastatic melanoma and NSCLC compared with ICI alone.,Furthermore, COXi use appears to reverse the negative prognostic effect of a high NLR by prolonging TTP in patients with melanoma.
Clinical features of Asian melanoma patients are distinct from those of Western patients.,This study was designed to determine the molecular and clinical characteristics of Asian melanoma patients treated with anti-PD-1 antibody.,Patients with recurrent or metastatic melanoma who began anti-PD-1 antibody therapy between January 2015 and April 2018 were retrospectively reviewed.,Patients who underwent next-generation sequencing were also analyzed.,A total of 152 patients were included.,The median age was 61 years, and 53% of patients were female.,A total of 56 patients (37%) received immunotherapy as second-line or greater chemotherapy.,Primary sites were acral (38%), mucosal (31%), cutaneous (24%), uveal (2%), and unknown (5%).,The overall response rate was 17% (95% CI, 11-22%), and disease control rate was 60% (95% CI, 52-68%).,The median progression-free survival (PFS) was 4.2 months (95% CI, 1.8-6.6 months), and median overall survival (OS) was 32.9 months (95% CI, 20.0-45.7 months).,However, BRAFV600 and KIT mutational statuses were not associated with response or survival.,High neutrophil-lymphocyte ratio (NLR) was associated with poor PFS (median PFS 6.9 vs.,2.4 months, p = 0.015) and OS (median OS NR vs.,10.4 months, p < 0.001).,In multivariate analysis, high NLR independently predicted poor survival.,This study includes the largest set of integrated genomic data analyzing Asian patients with melanoma treated with immunotherapy.,BRAF V600 and KIT mutational statuses were not associated with response or survival, and high NLR was a strong predictor of poor response to and survival with anti-PD-1 therapy.