Multinational study of real-world first-line treatment patterns and outcomes in patients with advanced non-small cell lung cancer

A retrospective study of patients in the Flatiron Health Enhanced Datamart diagnosed with advanced non-small cell lung cancer (NSCLC) between January 2019 and November 2023, with follow-up throug November 2024, investigated real-world first-line treatments and outcomes. Among 34,187 patients, median age was 70 years (65% White, 87% having a history of smoking). Median duration of first-line therapy was 121 days (IQR 42-337), with first-line PD-(L)1 therapy received by 57%. The median overall survival (OS) and real-world progression-free survival (rwPFS) among patients receiving first-line therapy (75%) were 15.4 months (95% CI 15.0-15.8) and 7.2 months (7.1-7.4), respectively. Outcomes improved with higher PD-L1 expression, with a median OS of 13.8 months (95% CI 13.1-14.5) for PD-L1 < 1% and 18.4 months (17.3-19.4) for PD-L1 ≥ 50%. Patients with KRAS-mutations and PD-L1 < 1% had a median OS less than 10 months. In multivariable analyses, PD-L1 < 1% compared with ≥ 50% (aHR 1.28; 95% CI 1.21-1.35) and KRAS non-G12C mutations compared with KRAS wild-type or unknown status (1.10; 1.05-1.166) were associated with increased mortality. A high-risk subgroup of patients with both KRAS-mutations and PD-L1 < 1% had increased risk of mortality compared with all othe patients (aHR 1.34; 95% CI 1.24-1.45). Similar trends were observed for rwPFS. The authors conclude that poor survival outcomes were observed across all first-line treatment options, with especially poor outcomes for patients with KRAS-mutations and low PD-L1 expression.