Clinical impact of continuing osimertinib beyond progression versus best supportive care in EGFR-mutated advanced non-small cell lung cancer: a multi-institutional retrospective study.

BACKGROUND: The optimal management of patients with epidermal growth factor receptor (EGFR)-mutated non-small-cell lung cancer (NSCLC) after progression on osimertinib includes cytotoxic chemotherapy. Continuing osimertinib therapy beyond progressive disease (PD) is occasionally adopted in real-world practice; however, evidence for its efficacy is limited. In this multi-institutional retrospective study, we evaluated whether osimertinib continuation beyond PD could improve survival compared with the best supportive care (BSC) in such patients. METHODS: We retrospectively reviewed patients with EGFR-mutated advanced or recurrent NSCLC treated with osimertinib between March 2016 and September 2025 at three Japanese community hospitals. Patients with radiological progression or intolerable adverse events after osimertinib treatment were included Patients were classified into three groups: (1) osimertinib beyond PD, (2) BSC, and (3) chemotherapy after osimertinib. Overall survival (OS) was compared among the groups using Kaplan-Meier and Cox regression analyses adjusted for time-to-treatment failure (TTF). RESULTS: Of the 309 patients treated with osimertinib, 126 met the inclusion criteria. The median age of the patients was 77 years, and 23% had poor performance status (≥ 2). Osimertinib beyond PD was administered to 21 patients (16.7%), BSC to 36 patients (28.6%), and chemotherapy to 69 patients (54.8%). The median OS after osimertinib failure was 8.8, 2.6, and 15.5 months in the beyond PD, BSC, and chemotherapy groups, respectively (p < 0.001). In multivariate analysis, beyond PD was associated with significantly longer OS than BSC (hazard ratio: 0.34, 95% confidence interval: 0.18-0.66, p < 0.001), even after adjusting for TTF. CONCLUSIONS: In real-world settings involving elderly and frail patients, osimertinib continuation beyond PD was associated with improved survival compared with BSC alone. Although chemotherapy remains the preferred strategy when feasible, osimertinib continuation beyond PD may represent a reasonable treatment option for patients who are ineligible for further cytotoxic therapy. In the absence of other guiding biomarkers, TTF may help clinicians identify patients most likely to benefit from continued TKI administration.