Real-World Outcomes and Progression Patterns with First-Line Osimertinib in Patients with Advanced EGFR-Mutant Non-Small Cell Lung Cancer: A Nationwide Turkish Oncology Group Study

Background/Objectives: We aimed to evaluate the real-world outcomes of first-line osimertinib in patients with advanced EGFR-mutant non-small cell lung cancer, together with the progression patterns, including the management and outcomes of oligoprogressive disease in the real-world setting. Methods: Patients who received first-line osimertinib at 33 oncology centers across Türkiye were retrospectively analyzed. Results: The median (IQR) age of 143 patients was 59.4 (50.9–68.9), 62.9% were female, and 68.5% were non-smokers. The most frequently identified EGFR mutations were exon 19 deletion (64.3%) and exon 21 L858R (28.7%). The median progression-free survival (PFS) was 17.6 months (95% CI 14.6–20.6). Exon 19 deletion subgroup had significantly longer median PFS than exon 21 L858R subgroup (22.0 vs. 11.7 months; HR = 0.40 95% CI 0.25–0.64; p < 0.001). Of the patients who experienced disease progression, 51.2% had oligoprogression. Among these, 81.8% received local ablative treatments (LATs) while continuing osimertinib. The median time to osimertinib discontinuation was significantly longer in patients treated with LATs than in those who continued osimertinib without LATs (8.5 vs. 3.0 months; p = 0.001). In the overall cohort, 12- and 24-month overall survival (OS) rates were 93.0% and 82.5%, respectively. The median OS was significantly longer in patients with oligoprogression compared to those with systemic progressive disease (57.7 vs. 36.5 months; p = 0.007). Any-grade and grade ≥ 3 osimertinib-related adverse events occurred in 55.2% and 6.3% of patients, respectively. Conclusions: This study supports the real-world effectiveness and tolerability of first-line osimertinib. Oligoprogression was associated with longer OS compared with systemic progression, and the integration of LATs in carefully selected patients with oligoprogression may be associated with prolonged osimertinib treatment duration and favorable post-progression outcomes.