Durvalumab after sequential chemoradiotherapy in unresectable stage III non-small-cell lung cancer-final analysis...

Durvalumab after concurrent chemoradiotherapy (cCRT) is the standard of care for patients with unresectable, stage III non-small-cell lung cancer (NSCLC). However, patients often receive sequential chemoradiotherapy (sCRT) due to factors including advanced age or frailty, comorbidities, or disease- or access-related concerns. The phase II PACIFIC-6 trial (NCT03693300) evaluated the safety of durvalumab after sCRT in this setting. Interim results indicated a similar safety profile to that observed with durvalumab after cCRT, with encouraging preliminary efficacy. We report outcomes from the final analysis.

Adults with unresectable, stage III NSCLC, Eastern Cooperative Oncology Group performance status ≤2, and no disease progression following platinum-based sCRT were enrolled to receive durvalumab 1500 mg intravenously once every 4 weeks for up to 24 months. The primary endpoint was the incidence of grade 3/4 adverse events (AEs) possibly related to treatment (PRAEs) occurring within 6 months. Secondary endpoints included overall survival (OS) and progression-free survival (PFS; investigator assessed as per RECIST v1.1).

As of 20 March 2023, 117 patients (65.8% aged ≥65 years; 98.3% with past or present comorbidities) were enrolled. Overall, 27.4% of patients had grade 3/4 AEs and 6.0% had grade 3/4 PRAEs, including two patients (1.7%) with pneumonitis. Three patients (2.6%) had fatal AEs, with one (0.9%) having a fatal PRAE (pneumonitis). Overall, 27.4% discontinued durvalumab due to AEs. Median follow-up was 32.6 and 30.2 months among patients censored for OS and PFS, respectively. Median OS was 39.0 months [95% confidence interval (CI) 30.6 months-not calculable]; 3-year OS rate was 56.5% (95% CI 46.4% to 65.5%). Median PFS was 13.1 months (95% CI 7.4-19.9 months); 2-year PFS rate was 35.3% (95% CI 26.5% to 44.3%).

Durvalumab after sCRT was well tolerated and could be an alternative treatment strategy when cCRT is not feasible. Confirmatory randomized phase III data are awaited.