Durvalumab After Concurrent Chemoradiotherapy in Elderly Patients With Unresectable Stage III Non-Small-Cell Lung Cancer (PACIFIC)

Mark A Socinski; Mustafa Özgüroğlu; Augusto Villegas; Davey Daniel; David Vicente; Shuji Murakami; Rina Hui; Jhanelle E Gray; Keunchil Park; Mark Vincent; Helen Mann; Michael Newton; Phillip A Dennis; Scott J Antonia

doi:10.1016/j.cllc.2021.05.009

Durvalumab After Concurrent Chemoradiotherapy in Elderly Patients With Unresectable Stage III Non-Small-Cell Lung Cancer (PACIFIC)

Clin Lung Cancer. 2021 Nov;22(6):549-561. doi: 10.1016/j.cllc.2021.05.009. Epub 2021 Jun 12.

Authors

Affiliations

¹ AdventHealth Cancer Institute, Orlando, FL. Electronic address: Mark.Socinski.MD@AdventHealth.com.
² Istanbul University-Cerrahpaşa, Cerrahpaşa School of Medicine, Istanbul, Turkey.
³ Cancer Specialists of North Florida, Jacksonville, FL.
⁴ Sarah Cannon Research Institute/Tennessee Oncology, Chattanooga, TN.
⁵ Hospital Universitario Virgen Macarena, Seville, Spain.
⁶ Kanagawa Cancer Center, Yokohama, Japan.
⁷ Westmead Hospital and the University of Sydney, Sydney, NSW, Australia.
⁸ Moffitt Cancer Center, Tampa, FL.
⁹ Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
¹⁰ London Health Sciences Centre, London, ON, Canada.
¹¹ AstraZeneca, Cambridge, UK.
¹² AstraZeneca, Gaithersburg, MD.

PMID: 34294595
DOI: 10.1016/j.cllc.2021.05.009

Abstract

Background: The PACIFIC trial demonstrated that consolidation durvalumab significantly improved PFS and OS (the primary endpoints) vs. placebo in patients with unresectable, stage III NSCLC whose disease had not progressed after platinum-based, concurrent chemoradiotherapy (CRT). We report exploratory analyses of outcomes from PACIFIC by age.

Patients and methods: Patients were randomized 2:1 (1-42 days post-CRT) to receive 12-months' durvalumab (10 mg/kg intravenously every-2-weeks) or placebo. We analyzed PFS and OS (unstratified Cox-proportional-hazards models), safety and patient-reported outcomes (PROs: symptoms, functioning, and global-health-status/quality-of-life) in subgroups defined by a post-hoc 70-year age threshold. Data cut-off for PFS was February 13, 2017 and for OS, safety and PROs was March 22, 2018.

Results: Overall, 158 of 713 (22.2%) and 555 of 713 (77.8%) randomized patients were aged ≥70 and <70 years, respectively. Durvalumab improved PFS and OS among patients aged ≥70 (PFS: hazard ratio [HR], 0.62 [95% CI, 0.41-0.95]; OS: HR, 0.78 [95% CI, 0.50-1.22]) and <70 (PFS: HR, 0.53 [95% CI, 0.42-0.67]; OS: HR, 0.66 [95% CI, 0.51-0.87]), although the estimated HR-95% CI for OS crossed one among patients aged ≥70. Durvalumab exhibited a manageable safety profile and did not detrimentally affect PROs vs. placebo, regardless of age; grade 3/4 (41.6% vs. 25.5%) and serious adverse events (42.6% vs. 25.5%) were more common with durvalumab vs. placebo among patients aged ≥70.

Conclusion: Durvalumab was associated with treatment benefit, manageable safety, and no detrimental impact on PROs, irrespective of age, suggesting that elderly patients with unresectable, stage III NSCLC benefit from treatment with consolidation durvalumab after CRT. However, small subgroup sizes and imbalances in baseline factors prevent robust conclusions.

Trial registration: ClinicalTrials.gov NCT02125461.

Keywords: Exploratory analysis; Immune-checkpoint inhibitors; Patient-reported outcomes; Safety; Survival.

Publication types

Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Aged
Antibodies, Monoclonal / administration & dosage*
Antineoplastic Agents, Immunological / administration & dosage*
Carcinoma, Non-Small-Cell Lung / drug therapy
Carcinoma, Non-Small-Cell Lung / pathology*
Chemoradiotherapy*
Humans
Lung Neoplasms / drug therapy*
Lung Neoplasms / pathology*
Male
Patient Reported Outcome Measures

Substances

Antibodies, Monoclonal
Antineoplastic Agents, Immunological
durvalumab

Associated data

ClinicalTrials.gov/NCT02125461