EGFR-TKI plus chemotherapy versus TKI monotherapy in advanced EGFR-mutant NSCLC with high PD-L1 expression: a real-world retrospective study.

[BACKGROUND] Patients with advanced EGFR-mutant NSCLC and high PD-L1 expression (TPS ≥50%) typically respond poorly to EGFR-TKI monotherapy. We compared EGFR-TKI plus chemotherapy versus TKI alone in this population.

[RESEARCH DESIGN AND METHODS] This retrospective study included 212 patients receiving first-line osimertinib with chemotherapy ( = 98) or as monotherapy ( = 114). Primary endpoint was progression-free survival (PFS).

[RESULTS] Combination therapy significantly improved median PFS overall (22.5 vs 13.8 months; HR = 0.513, 95% CI:0.372-0.803;  < 0.001) and in PD-L1-high patients (18.2 vs 7.9 months; HR = 0.356, 95% CI:0.195-0.641;  = 0.001). ORR was higher with combination therapy (67.3% vs 36.8%;  < 0.001). Grade ≥3 adverse events were more common with combination therapy (45.9% vs 22.8%) but were primarily manageable hematological events.

[CONCLUSIONS] Osimertinib-chemotherapy combination showed superior efficacy versus monotherapy in EGFR-mutant, PD-L1-high NSCLC, with manageable safety. Our real-world findings validate and extend the FLAURA2 results by highlighting this high-risk subgroup as one that may derive particular benefit from first-line combination therapy.