Lung cancer (Amsterdam, Netherlands) · 2026
First-line treatment patterns and real-world outcomes in patients with advanced KRAS-mutated non-small cell lung cancer with high unmet need.
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Barlesi Fabrice, Skoulidis Ferdinandos, Solomon Benjamin, Lee Joowon, Jassim Rami, Gupta Ravi, Mesa-Frias Marco, Felip Enriqueta
Аннотация
BACKGROUND: This study aims to describe real-world patient characteristics and treatment patterns for advanced non-small cell lung cancer (NSCLC) and estimate overall survival (OS) and real-world progression-free survival (rwPFS) in those receiving first-line (1 L) treatment.
PATIENTS AND METHODS: In a retrospective study of patients in the Flatiron Health Enhanced Datamart diagnosed with advanced NSCLC between January 1, 2019, and November 30, 2023, with follow-up through November 30, 2024, OS and rwPFS were assessed from initiation of 1 L therapy. Survival was evaluated using Kaplan-Meier method and Cox proportional hazards models adjusting for key covariates.
RESULTS: Among 34,187 patients identified, median age was 70 years, with the majority being White (65%) and having a history of smoking (87%). Median duration of 1 L therapy was 121 days (IQR, 42-337), with 1 L PD-(L)1 therapy received by 14,603 (57%) patients. The median OS and rwPFS among patients receiving 1 L therapy (25,512 [75%] patients) were 15.4 months (95% CI, 15.0-15.8) and 7.2 months (95% CI, 7.1-7.4), respectively. Outcomes improved with higher PD-L1 expression, with a median OS of13.8 months (95% CI, 13.1-14.5) for PD-L1 < 1% vs 18.4 months (95% CI, 17.3-19.4) for PD-L1 ≥ 50% (p < 0.001). Patients with KRAS-mutations and PD-L1 < 1% had a median OS of less than10 months. In multivariable analyses, PD-L1 < 1% compared with ≥ 50% and KRAS non-G12C mutations compared with KRAS wild-type or unknown status were associated with increased mortality (adjusted hazard ratio [aHR], 1.28 [95% CI, 1.21-1.35] and 1.10[95% CI, 1.05-1.16]; both p < 0.001). A high-risk subgroup of patients with both KRAS-mutations and PD-L1 < 1% had an increased risk of mortality compared with all other patients (aHR, 1.34 [95% CI, 1.24-1.45]; p < 0.001). Similar trends were observed for rwPFS.
CONCLUSIONS: Poor survival outcomes were observed across all 1 L treatment options. Patients with KRAS-mutated NSCLC and low PD-L1 expression had especially poor outcomes, highlighting the need for more effective treatment options.
PATIENTS AND METHODS: In a retrospective study of patients in the Flatiron Health Enhanced Datamart diagnosed with advanced NSCLC between January 1, 2019, and November 30, 2023, with follow-up through November 30, 2024, OS and rwPFS were assessed from initiation of 1 L therapy. Survival was evaluated using Kaplan-Meier method and Cox proportional hazards models adjusting for key covariates.
RESULTS: Among 34,187 patients identified, median age was 70 years, with the majority being White (65%) and having a history of smoking (87%). Median duration of 1 L therapy was 121 days (IQR, 42-337), with 1 L PD-(L)1 therapy received by 14,603 (57%) patients. The median OS and rwPFS among patients receiving 1 L therapy (25,512 [75%] patients) were 15.4 months (95% CI, 15.0-15.8) and 7.2 months (95% CI, 7.1-7.4), respectively. Outcomes improved with higher PD-L1 expression, with a median OS of13.8 months (95% CI, 13.1-14.5) for PD-L1 < 1% vs 18.4 months (95% CI, 17.3-19.4) for PD-L1 ≥ 50% (p < 0.001). Patients with KRAS-mutations and PD-L1 < 1% had a median OS of less than10 months. In multivariable analyses, PD-L1 < 1% compared with ≥ 50% and KRAS non-G12C mutations compared with KRAS wild-type or unknown status were associated with increased mortality (adjusted hazard ratio [aHR], 1.28 [95% CI, 1.21-1.35] and 1.10[95% CI, 1.05-1.16]; both p < 0.001). A high-risk subgroup of patients with both KRAS-mutations and PD-L1 < 1% had an increased risk of mortality compared with all other patients (aHR, 1.34 [95% CI, 1.24-1.45]; p < 0.001). Similar trends were observed for rwPFS.
CONCLUSIONS: Poor survival outcomes were observed across all 1 L treatment options. Patients with KRAS-mutated NSCLC and low PD-L1 expression had especially poor outcomes, highlighting the need for more effective treatment options.