Durvalumab after sequential chemoradiotherapy in stage III, unresectable NSCLC: the phase 2 PACIFIC-6 trial

Abstract

Background: Based on the findings of the phase 3 PACIFIC trial (NCT02125461), durvalumab is standard of care for patients with stage III, unresectable NSCLC and no disease progression following concurrent chemoradiotherapy (cCRT). Many patients are considered unsuitable for cCRT due to concerns with tolerability. The phase 2 PACIFIC-6 trial (NCT03693300) evaluates the safety and tolerability of durvalumab following sequential CRT (sCRT). Methods: Patients with stage III, unresectable NSCLC and no progression following platinum-based, sCRT were enrolled to receive durvalumab (1500 mg intravenously) every 4 weeks for up to 24 months. The primary endpoint was the incidence of grade 3/4 adverse events possibly related to treatment (PRAEs) occurring within 6 months. Secondary endpoints included investigator-assessed progression-free survival (PFS; RECIST v1.1) and overall survival (OS). Results: Overall, 117 patients were enrolled (59.8% with PS >0, 65.8% aged ≥65 years, and 37.6% with stage IIIA disease). Median treatment duration was 32.0 weeks; 37.6% of patients remained on treatment at data cut-off (July 15, 2021). Grade 3/4 AEs occurred in 18.8% of patients. Five patients had grade 3/4 PRAEs within 6 months (incidence: 4.3%; 95% CI: 1.4-9.7), including two pneumonitis cases. Two patients (1.7%) had grade 5 AEs of any cause. Survival data maturity was limited. Median PFS was 10.9 months (95% CI: 7.3-15.6) and 12-month PFS and OS rates were 49.6% and 84.1%, respectively. Conclusions: Durvalumab following sCRT had a comparable safety profile to that observed with durvalumab following cCRT in PACIFIC and showed encouraging preliminary efficacy in a frailer population.