PACIFIC-5: a phase III clinical trial of consolidation durvalumab in patients with unresectable stage III NSCLC and no progression after concurrent or sequential chemoradiotherapy.

BACKGROUND

Consolidation durvalumab following no progression on concurrent chemoradiotherapy (cCRT) is standard of care for unresectable stage III non-small-cell lung cancer (NSCLC). However, in clinical practice many patients receive sequential CRT (sCRT). The PACIFIC-5 trial aimed to evaluate the efficacy and safety of consolidation durvalumab for unresectable stage III NSCLC following no progression on cCRT or sCRT.

METHODS

This randomised, double-blind, placebo-controlled, phase III trial enrolled patients aged ≥ 18 years with unresectable stage III NSCLC, regardless of PD-L1 expression or sensitising EGFR or ALK aberrations, without disease progression after cCRT or sCRT. Patients were randomised (2:1) to durvalumab 1500 mg or placebo intravenously every 4 weeks (stratified by tumour PD-L1 expression and prior treatment) until disease progression, unacceptable toxicity, or consent withdrawal. The primary endpoint was progression-free survival (PFS) by blinded independent central review in the modified intention-to-treat population (mITT). Secondary endpoints included overall survival (OS) in the mITT and safety. The safety analysis set include patients who received at least one dose of study treatment.

RESULTS

Of 407 patients randomised to receive durvalumab (n = 272) or placebo (n = 135), 405 received at least one dose of durvalumab (n = 271) or placebo (n = 134). The mITT comprised 381 patients randomised to durvalumab (n = 252) or placebo (n = 129). Durvalumab showed statistically significant improvement in PFS versus placebo in the mITT (median [95% confidence interval {CI}], 14.0 [10.9-18.0] vs. 6.5 [5.4-13.8] months; hazard ratio [95% CI], 0.75 [0.58-0.99]; p = 0.038). There was a trend toward improved OS with durvalumab versus placebo in the mITT (median [95% CI], 38.3 [28.9-42.8] vs. 32.5 [20.6-40.4] months; hazard ratio [95% CI], 0.87 [0.66-1.17]; p = 0.346 [interim analysis]). Among the safety analysis set, maximum grade 3 or 4 adverse events of any cause occurred in 26.9% (73/271) and 23.9% (32/134) and 1.5% (4/271) and 0% (0/134) had treatment-related adverse events leading to death for durvalumab and placebo, respectively.

CONCLUSIONS

PACIFIC-5 met its primary endpoint of improved PFS after either cCRT or sCRT. Follow-up for overall survival is ongoing.

TRIAL REGISTRATION: NCT03706690.