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
Year: 2025
Type: article
Study design: Clinical Trial
Abstract: 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.
Source: Journal of Hematology & Oncology
Authors: Yi-Long Wu, Lin Wu, Nan Bi, Timucin Cil, Hong Ge, Zhengfei Zhu, Chih-Liang Wang, Wei Zhang, Dongqing Lv, E. Mingyan, Jianguo Sun, Yi Pan, Maciej Krzakowski, Mustafa Dikilitas, Mehmet Ali Nahit Sendur, Young-Chul Kim, Yanjiao Yang, Rui Mao, Biao Zhang, Luhua Wang
Institutions: Guangdong Academy of Medical Sciences, Guangdong Provincial People's Hospital, Southern Medical University, Central South University, Hunan Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, State Key Laboratory of Molecular Oncology, Zhengzhou University, Henan Cancer Hospital, Shanghai Medical College of Fudan University, Fudan University, Fudan University Shanghai Cancer Center, Chang Gung Memorial Hospital, Taoyuan Chang Gung Memorial Hospital, Linkou Chang Gung Memorial Hospital, Tongji University, Shanghai Pulmonary Hospital, Wenzhou Medical University, Zhejiang Taizhou Hospital, Harbin Medical University, Third Affiliated Hospital of Harbin Medical University, Army Medical University, The Maria Sklodowska-Curie National Research Institute of Oncology, Inonu University, Ankara Yıldırım Beyazıt University, Ankara Bilkent City Hospital, Chonnam National University Hwasun Hospital
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $4,990
OpenAlex ID: W4417097041