Consolidation Osimertinib versus Durvalumab versus Observation following Concurrent Chemoradiation in Unresectable EGFR-Mutant Non-Small-Cell Lung Cancer: A Multicenter Retrospective Cohort Study

Introduction Durvalumab improves survival when used as consolidation therapy after chemoradiation (CRT) in patients with stage III NSCLC. However, the optimal consolidation therapy for patients with EGFR-mutant (EGFRmut) stage III NSCLC remains unknown. Methods In this multi-institutional international retrospective analysis across 24 institutions, we evaluated outcomes in patients with stage III EGFRmut NSCLC treated with concurrent CRT followed by consolidation therapy with osimertinib, durvalumab, or observation between 2015 and 2022. Kaplan-Meier method was used to estimate real-world progression-free survival (rwPFS, primary endpoint) and overall survival (OS, secondary endpoint). Treatment-related adverse events (trAE) during consolidation treatment were defined using Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Multivariable Cox regression analysis was used. Results Of 136 patients with stage III EGFRmut NSCLC treated with definitive concurrent CRT, 56 received consolidation durvalumab, 33 received consolidation osimertinib, and 47 received observation alone. Baseline characteristics were similar across the 3 cohorts. With a median follow-up of 46 months for the entire cohort, the median duration of treatment was not reached (NR) for osimertinib (Inter-quartile range [IQR]: NR-NR) and was 5.5 (IQR:2.4-10.8) months with durvalumab. After adjusting for nodal status, stage III A/B/C, and age, patients treated with consolidation osimertinib had significantly longer 24-month rwPFS compared to those in the durvalumab or observation cohorts (osimertinib: 86%, durvalumab: 30%, observation: 27%, p<0.001 for both comparisons). There was no difference in rwPFS between durvalumab and the observation cohort. No significant difference in OS across the 3 cohorts was detected, possibly due to the limited follow-up. Any grade trAE occurred in 52% (2 [6.1%] grade ≥3) and 48% (10 [18%] grade ≥3) of patients treated with osimertinib and durvalumab, respectively. Of 45 patients who progressed on consolidation durvalumab, 37 (82%) subsequently received EGFR tyrosine kinase inhibitors (TKIs). Of these, 14 (38%) patients developed trAEs including 5 pneumonitis (14%; 2 [5.4%] grade ≥3) and 5 diarrhea (14%; 1 [2.7%] grade ≥3). Conclusions This study suggests that among patients with stage III unresectable NSCLC with a sensitizing EGFR mutation, consolidation osimertinib was associated with significantly longer rwPFS than durvalumab or observation. No unanticipated safety signals were observed with consolidation osimertinib.