Risk Factors Associated with Suboptimal Real-World Outcomes in Patients with EGFR-Mutated Non-Small Cell Lung Cancer Treated with Front-Line Recommended Therapy.

Introduction: Osimertinib, a recommended front-line (1L) treatment option for non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations [exon 19 deletion (ex19del)/exon 21 L858R substitution (L858R)], demonstrated significantly improved progression-free survival and overall survival (OS) compared with other EGFR tyrosine kinase inhibitors in the FLAURA trial. However, most patients developed secondary resistance, and subpopulations experienced disparate outcomes. This retrospective, observational study aimed to describe real-world treatment outcomes along with patient clinical characteristics associated with different clinical outcomes among patients with EGFR-mutated (ex19del/L858R) NSCLC who received osimertinib as 1L therapy.

Methods: This retrospective cohort study of patient clinical and genomic data from a de-identified, US-based, nationwide NSCLC clinico-genomic database evaluated OS, time-to-next-treatment (TTNT), and time-to-discontinuation (TTD) among patients with EGFR-mutated NSCLC who received 1L osimertinib monotherapy and identified patient characteristics associated with differences in clinical outcomes as related to real-world 1L osimertinib use.

Results: Among 703 identified patients, mean age was 69 years, 67% of patients were female, and 53% were White. Median OS was 29.8 months, TTNT was 17.6 months, and TTD was 15.9 months. A large majority of the overall population had risk factors associated with suboptimal real-world outcomes (97% for OS, 95% for TTNT, and 87% for TTD), even among patients with ECOG PS scores of 0-1. Key individual risk factors identified included metastases of the liver, bone, and central nervous system; ECOG PS scores ≥ 2; and TP53, CDK-4, and EGFR L858R mutations.

Conclusions: More than 90% of the assessed real-world patients with EGFR-mutated (ex19del/L858R) NSCLC who received 1L osimertinib had risk factors associated with suboptimal outcomes, highlighting the urgent unmet need for new treatments and emphasizing the importance of administering the most effective therapy in the 1L setting.