Immune checkpoint inhibitors (ICIs) have become a cornerstone in the treatment of advanced non-small cell lung cancer (NSCLC). In the pivotal Keynote-024 study with highly selected patients, pembrolizumab improved survival compared with platinum-based chemotherapy (CT) in patients with a PD-L1 tumor proportion score ≥50% (median overall survival (mOS) 26.3 months and 1-year survival 70%) and treatment-related adverse events were less frequent compared to CT. Recent real-world studies show comparable results with the exception of patients with poor performance status (PS).
Data were collected retrospectively from consecutive patients treated in first-line with ICI from March 2017 to October 2018 in a nationwide oncology study. Clinical data included gender, age, smoking status, ECOG PS, TNM stage, histology, metastatic sites, comorbidity and reasons for treatment cessation and adverse events that caused hospitalization or death. Overall survival was assessed using Kaplan-Meier estimates and the association to clinical features determined by a multivariate Cox’s proportional hazards regression model.
A total of 578 stage III-IV NSCLC patients were included. Median age was 69.8 years (range 45 – 88) and 43% were male. Tumors were predominantly adenocarcinomas (71%), and 82% of patients had stage IV disease. At baseline metastases to the brain, bones, and liver were observed in 7%, 28% and 11% of patients, respectively. Fifteen percent of patients had PS ≥2. Median OS was 19.6 months (95%CI 16.6-23.6), and estimated 1-year survival was 63.7%. In the multivariate analysis, patients with PS ≥2 (HR 1.7; 95%CI 1.2-2.3; P=0.002), bone metastases (HR 1.8; 95%CI 1.4-2.4; P=0.00) and liver metastases (HR 1.5; 95%CI 1.1-2.2; P=0.02) had a significantly worse prognosis. Age ≥75 years, sex, smoking status, histology, and Charlson Comorbidity Index Score were not significantly associated with OS.
A slightly poorer mOS and 1-year survival of real-world NSCLC patients compared to randomized trials was explained primarily by treatment of patients with PS ≥2 and metastases to the liver and bones. Age ≥75 years was not associated with a poor outcome.