Durvalumab after concurrent chemoradiotherapy for sensitizing epidermal growth factor receptor-mutant stage III...

In locally advanced epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC), the efficacy and safety of durvalumab after concurrent chemoradiotherapy (CCRT) remain controversial.

In this retrospective cohort study, we analyzed treatment outcomes in patients with unresectable stage III sensitizing EGFR-mutant NSCLC who underwent and completed CCRT without progression between July 2015 and June 2022 from 48 institutions in Japan. Patients with confirmed EGFR mutations after recurrence were excluded. Comparisons between groups were conducted using a cohort extracted through propensity score matching (PSM). The primary outcome was progression-free survival (PFS). The secondary outcomes were overall survival (OS) and safety of EGFR-tyrosine kinase inhibitor (TKIs) after durvalumab treatment.

Out of 162 eligible patients, 106 received consolidation durvalumab following CCRT and 56 did not. After PSM, 56 patients were matched to the durvalumab and CCRT alone groups. The median PFS was significantly longer in patients treated with durvalumab than in those treated with CCRT alone (26.8 months [95 % confidence interval [CI], 13.9-NA] vs. 11.1 months [95 % CI, 9.0-18.2]; hazard ratio [HR], 0.52 [95 % CI, 0.33-0.83]; p = 0.005). While early osimertinib administration following durvalumab tended to increase Common Terminology Criteria for Adverse Events (CTCAE) grade ≥ 3 pneumonitis, there was no significant difference in the frequency of CTCAE grade ≥ 3 adverse events with EGFR-TKIs between the groups (23.5 % vs. 20.8 %).

Durvalumab administration following CCRT prolongs PFS in patients with locally advanced EGFR-mutant NSCLC. Durvalumab can be safely administered if the timing of subsequent osimertinib is carefully managed.