Dual immune checkpoint inhibition vs anti–PD-1 monotherapy in metastatic <i>BRAF</i> wild-type/undetermined melanoma: Ethnicity-based benchmarking of treatment endpoints in 2,659 patients.

Abstract

e21512 Background: Immunotherapy is the mainstay for metastatic melanoma (MM), yet ethnic differences in treatment outcomes remain underexplored courtesy due to inconsistent reporting. Our systematic review and meta-analysis assessed overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) among BRAF wild-type/undetermined MM patients receiving anti-PD1 monotherapy (nivolumab or pembrolizumab) or dual immune checkpoint inhibition (nivolumab plus ipilimumab), focusing on ethnicity based benchmarking. Methods: PubMed, Embase, and Cochrane Central were searched for real world studies reporting outcomes in adults with BRAF wild-type or undetermined MM treated with first-line anti-PD1 monotherapy or dual checkpoint inhibition. Meta-analysis using a random-effects model was conducted for the aforesaid treatment endpoints. Results: 2,659 patients from 8 studies were included for analysis. Median ages ranged from 62 to 75 years. Majority of patients had good performance status (ECOG 0-1). OS and PFS were summarised qualitatively due to limited hazard ratio data. Median OS for anti-PD1 monotherapy (n=595) was 31.5 months, with Asians demonstrating lower survival (28.1 months) compared with White patients (32.5 months). Dual checkpoint inhibition (n=417) was associated with a longer median OS (58.3 months), although markedly shorter among Asians (12 months) relative to Whites (59.2 months). Median PFS followed a similar pattern, with anti-PD1 monotherapy yielding 7.6 months overall (Asians 6.1; Whites 8.2) and dual therapy 17.8 months overall (Asians 8.2; Whites 18.8). Meta-analysis of ORR included 1,757 patients, demonstrating a higher pooled response for dual therapy (52%) than for monotherapy (36%). Among White patients, dual therapy achieved higher ORR (57.2%) (n=682) than monotherapy (36.9%) (n=902), whereas Asians had comparable responses to either regimen [(37.5% for dual (n=40); 35.3% for monotherapy (n=144)]. Differences between ethnic subgroups did not reach statistical significance. No eligible studies reported outcomes for Black or mixed-ethnicity populations, precluding quantitative or qualitative analyses in these groups. Conclusions: Dual checkpoint inhibition confers superior ORR compared with anti-PD1 monotherapy, particularly in White patients, whereas response among Asian patients appears similar across treatments. Across included studies, dual therapy was associated with a longer median OS of 58.3 months versus a median OS of 31.5 months with anti-PD1 monotherapy, dual therapy also demonstrates improved PFS of 17.8 months as compared to 7.6 months shown with monotherapy. Limited data on Black and Mixed ethnicities highlights the need for larger, ethnically diverse studies to guide optimised, personalised treatment.