The efficacy of pembrolizumab vs nivolumab plus ipilimumab in metastatic NSCLC in relation to PD-L1 and TMB status

BackgroundThe efficacy of immune checkpoint inhibitor (ICI) therapy concerning programmed death ligand 1 (PD-L1) status is well established in patients diagnosed with non-small cell lung cancer (NSCLC). However, there remains a paucity of evidence regarding the efficacy concerning tumor mutational burden (TMB) in both clinical trials and real-world data (RWD).MethodsWe established an Israeli multi-center registry for patients diagnosed with advanced and metastatic NSCLC between January 2018 and December 2022. Clinicopathological and molecular epidemiological data were meticulously collected, and treatment modalities were meticulously recorded. Clinical endpoints were evaluated using Kaplan-Meier curves and Cox-regression models according to treatment assignment.ResultsThe final analysis included a study population of 194 patients. Median age was 67 years (range 37-86), with the majority being male (71.13%), and 85.71% of patients were either current or former smokers at diagnosis. Adenocarcinoma accounted for most diagnoses (71.65%), followed by squamous cell carcinoma (24.23%). In terms of PD-L1 status, 42.78% had an expression level below 1%, 28.35% had an expression between 1-49%, and 28.87% had an expression above 50%. The median TMB ranged from 0 to 75, with a median of 10.31 (range 0-75) for PD-L1 expression below 1%, with a median of 9.73 (range 0.95-39.63) for PD-L1 expression between 1-49%, and a median of 9.72 (range 0.95-48) for PD-L1 expression above 50%. Corresponding to patients with low PDL-1 less than 1% and low TMB (0-5), the median overall survival (mOS) was 16 (p=0.18), and 15 months (p=0.22), patients with medium PDL-1 (1-49%) and medium TMB (5-10), the mOS was 15 (p=0.18) and 16 months (p=0.22), patients with high PDL-1 (>50) and high TMB (>10), the mOS was 21(p=0.18) and 24 (p=0.22) months.ConclusionsThis study represents the largest academic RWD dataset concerning PD-L1 and TMB status in patients with locally advanced and metastatic NSCLC. Although indirect comparisons suggest a comparable survival benefit.Legal entity responsible for the studyThe authors.FundingHas not received any funding.DisclosureAll authors have declared no conflicts of interest.