Outcomes with durvalumab after chemoradiotherapy in stage IIIA-N2 non-small-cell lung cancer: an exploratory analysis from the PACIFIC trial

ESMO Open

article

S. Senan¹  M. Özgüroğlu²  D. Daniel³  A. Villegas⁵  D. Vicente⁶  S. Murakami⁷  R. Hui⁸  C. Faivre-Finn⁹  L. Paz-Ares^1,10  Y.L. Wu^1,11  H. Mann^1,12  P.A. Dennis^1,12  S.J. Antonia^1,13 

[1]Department of Radiation Oncology, Amsterdam University Medical Centers, Vrije Universiteit Amsterdam, Cancer Center Amsterdam

[2]Istanbul University—Cerrahpaşa, Cerrahpaşa School of Medicine

[3]Tennessee Oncology

[4]Sarah Cannon Research Institute

[5]Cancer Specialists of North Florida

[6]Hospital Universitario Virgen Macarena

[7]Kanagawa Cancer Center

[8]Westmead Hospital and the University of Sydney

[9]The University of Manchester and The Christie NHS Foundation Trust

[10]Universidad Complutense, CiberOnc, CNIO and Hospital Universitario 12 de Octubre

[11]Guangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital & Guangdong Academy of Medical Sciences

[12]AstraZeneca

[13]H. Lee Moffitt Cancer Center and Research Institute

关键词: immunotherapy;    radiation therapy;    chemotherapy;    surgery;    multimodality therapy;   

DOI  :  10.1016/j.esmoop.2022.100410

学科分类：社会科学、人文和艺术（综合）

来源: BMJ Publishing Group

【 摘 要 】

Background The phase III PACIFIC trial (NCT02125461) established consolidation durvalumab as standard of care for patients with unresectable, stage III non-small-cell lung cancer (NSCLC) and no disease progression following chemoradiotherapy (CRT). In some cases, patients with stage IIIA-N2 NSCLC are considered operable, but the relative benefit of surgery is unclear. We report a post hoc, exploratory analysis of clinical outcomes in the PACIFIC trial, in patients with or without stage IIIA-N2 NSCLC.Materials and methods Patients with unresectable, stage III NSCLC and no disease progression after ≥2 cycles of platinum-based, concurrent CRT were randomized 2 : 1 to receive durvalumab (10 mg/kg intravenously; once every 2 weeks for up to 12 months) or placebo, 1-42 days after CRT. The primary endpoints were progression-free survival (PFS; assessed by blinded independent central review according to RECIST version 1.1) and overall survival (OS). Treatment effects within subgroups were estimated by hazard ratios (HRs) from unstratified Cox proportional hazards models.Results Of 713 randomized patients, 287 (40%) had stage IIIA-N2 disease. Baseline characteristics were similar between patients with and without stage IIIA-N2 NSCLC. With a median follow-up of 14.5 months (range: 0.2-29.9 months), PFS was improved with durvalumab versus placebo in both patients with [HR = 0.46; 95% confidence interval (CI), 0.33-0.65] and without (HR = 0.62; 95% CI 0.48-0.80) stage IIIA-N2 disease. Similarly, with a median follow-up of 25.2 months (range: 0.2-43.1 months), OS was improved with durvalumab versus placebo in patients with (HR = 0.56; 95% CI 0.39-0.79) or without (HR = 0.78; 95% CI 0.57-1.06) stage IIIA-N2 disease. Durvalumab had a manageable safety profile irrespective of stage IIIA-N2 status.Conclusions Consistent with the intent-to-treat population, treatment benefits with durvalumab were confirmed in patients with stage IIIA-N2, unresectable NSCLC. Prospective studies are needed to determine the optimal treatment approach for patients who are deemed operable.

【 授权许可】

CC BY|CC BY-NC-ND