Yi‐Long Wu, Lin Wu, Nan Bi, Timuçin Çil, Hong Ge, Zhengfei Zhu, Chih‐Liang Wang, Wei Zhang, Dongqing Lv, E Mingyan, Jianguo Sun, Yi Pan, Maciej Krzakowski, Mustafa Dikilitaş, Mehmet Ali Nahit Sendur, Young‐Chul Kim, Yanjiao Yang, Rui Mao, Biao Zhang, Lühua Wang
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.