For patients with unresectable stage III non-small-cell lung cancer (NSCLC), durvalumab given as consolidation treatment after concurrent chemoradiotherapy (cCRT) without disease progression has become the worldwide standard approach. Nevertheless, many individuals in real-world settings are treated with sequential chemoradiotherapy (sCRT) instead. The PACIFIC-5 study was therefore initiated to examine the clinical effectiveness and tolerability of consolidation durvalumab in this population following either cCRT or sCRT without progression. This global phase III trial used a randomised, double-blind, placebo-controlled design. It included adults (≥ 18 years) diagnosed with unresectable stage III NSCLC who had stable disease after completing cCRT or sCRT, regardless of PD-L1 levels or sensitising EGFR/ALK mutations. Participants were allocated in a 2:1 ratio to durvalumab (1500 mg IV every 4 weeks) or matching placebo, stratified by PD-L1 tumour expression and type of prior chemoradiotherapy. Therapy continued until progression, severe toxicity, or patient withdrawal. The main outcome was progression-free survival (PFS) determined by blinded independent central review within the modified intention-to-treat (mITT) group. Additional outcomes covered overall survival (OS) in the mITT population along with safety evaluations. Safety was analysed in all patients who received ≥ 1 dose of the study medication. In total, 407 individuals were randomised (272 to durvalumab and 135 to placebo), with 405 ultimately receiving treatment (271 and 134, respectively). The mITT analysis set included 381 patients (252 on durvalumab, 129 on placebo). Treatment with durvalumab led to a meaningful extension of PFS relative to placebo in the mITT group (median 14.0 months [95% CI: 10.9–18.0] compared with 6.5 months [95% CI: 5.4–13.8]; HR: 0.75 [95% CI: 0.58–0.99]; P = 0.038). An encouraging but non-significant trend was observed for OS (median 38.3 months [95% CI: 28.9–42.8] vs 32.5 months [95% CI: 20.6–40.4]; HR: 0.87 [95% CI: 0.66–1.17]; P = 0.346 at interim analysis). Grade 3/4 adverse events from any cause arose in 26.9% (73/271) of the durvalumab arm and 23.9% (32/134) of the placebo arm. Fatal treatment-related adverse events occurred in 1.5% (4/271) and 0% (0/134) of patients, respectively. The PACIFIC-5 trial achieved its primary goal by demonstrating improved PFS with durvalumab consolidation after either chemoradiotherapy regimen. Continued monitoring for overall survival differences is underway.
