Symptomatic Pneumonitis With Durvalumab After Concurrent Chemoradiotherapy in Unresectable Stage III NSCLC

Johan F. Vansteenkiste, MD, PhD; Jarushka Naidoo, MB, BCH, MHS; Corinne Faivre-Finn, MD, PhD; Mustafa Özgüroğlu, MD; Augusto Villegas, MD; Davey Daniel, MD; Shuji Murakami, MD; Rina Hui, M.B.B.S., PhD; Ki Hyeong Lee, MD; Byoung Chul Cho, MD, PhD; Kaoru Kubota, MD, PhD; Helen Broadhurst, MSc; Catherine Wadsworth, BVSc; Michael Newton, PharmD; Piruntha Thiyagarajah, MD; Scott J. Antonia, MD

JTO Clinical and Research Reports (Mar 2024)

Symptomatic Pneumonitis With Durvalumab After Concurrent Chemoradiotherapy in Unresectable Stage III NSCLC

Johan F. Vansteenkiste, MD, PhD,
Jarushka Naidoo, MB, BCH, MHS,
Corinne Faivre-Finn, MD, PhD,
Mustafa Özgüroğlu, MD,
Augusto Villegas, MD,
Davey Daniel, MD,
Shuji Murakami, MD,
Rina Hui, M.B.B.S., PhD,
Ki Hyeong Lee, MD,
Byoung Chul Cho, MD, PhD,
Kaoru Kubota, MD, PhD,
Helen Broadhurst, MSc,
Catherine Wadsworth, BVSc,
Michael Newton, PharmD,
Piruntha Thiyagarajah, MD,
Scott J. Antonia, MD

Affiliations

Johan F. Vansteenkiste, MD, PhD: Respiratory Oncology Unit and Trial Unit, Department of Respiratory Diseases, University Hospitals KU Leuven, Leuven, Belgium; Corresponding author. Address for correspondence: Johan F. Vansteenkiste, MD, PhD, Respiratory Oncology Unit (Respiratory Medicine), University Hospitals KU Leuven, Herestraat 49, Belgium.
Jarushka Naidoo, MB, BCH, MHS: Department of Medicine, Sidney Kimmel Comprehensive Cancer Center and Bloomberg–Kimmel Institute for Cancer Immunotherapy at Johns Hopkins University, Baltimore, Maryland; Department of Medicine, Beaumont Hospital and RCSI University of Health Sciences, Dublin, Ireland
Corinne Faivre-Finn, MD, PhD: Division of Cancer Sciences, and Clinical Oncology, The University of Manchester and The Christie NHS Foundation Trust, Manchester, United Kingdom
Mustafa Özgüroğlu, MD: Division of Medical Oncology, Istanbul University − Cerrahpaşa, Cerrahpaşa School of Medicine, Istanbul, Turkey
Augusto Villegas, MD: Hematology and Oncology, Cancer Specialists of North Florida, Jacksonville, Florida
Davey Daniel, MD: Oncology, Tennessee Oncology, Chattanooga, Tennessee, and Sarah Cannon Research Institute, Nashville, Tennessee
Shuji Murakami, MD: Department of Thoracic Oncology, Kanagawa Cancer Center, Yokohama, Japan
Rina Hui, M.B.B.S., PhD: Medical Oncology, Westmead Hospital and the University of Sydney, Sydney, NSW, Australia
Ki Hyeong Lee, MD: Internal Medicine Department, Chungbuk National University Hospital, Chungbuk National University College of Medicine, Cheongju, Republic of Korea
Byoung Chul Cho, MD, PhD: Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea
Kaoru Kubota, MD, PhD: Department of Pulmonary Medicine and Oncology, Nippon Medical School Hospital, Tokyo, Japan
Helen Broadhurst, MSc: Statistics, Plus-Project Ltd., Alderley Park, United Kingdom
Catherine Wadsworth, BVSc: Global Medicines Development, AstraZeneca, Alderley Park, United Kingdom
Michael Newton, PharmD: Late Development Oncology, AstraZeneca, Gaithersburg, Maryland
Piruntha Thiyagarajah, MD: Late Development Oncology, AstraZeneca, Cambridge, United Kingdom
Scott J. Antonia, MD: Department of Thoracic Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida

Journal volume & issue: Vol. 5, no. 3
p. 100638

Abstract

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Introduction: In the placebo-controlled, phase 3 PACIFIC trial, durvalumab significantly prolonged progression-free survival (PFS) (p < 0.0001) and overall survival (OS) (p = 0.00251) in patients with unresectable stage III NSCLC and no progression after platinum-based concurrent chemoradiotherapy (cCRT). Pneumonitis or radiation pneumonitis (PRP) was common in both arms. We report exploratory analyses evaluating the association of symptomatic (grade ≥2) PRP (G2+PRP) with baseline factors and clinical outcomes. Methods: Patients with WHO performance status of 0 or 1 were randomized (2:1) to 12 months of durvalumab or placebo, 1 to 42 days after cCRT. Associations between baseline factors and on-study G2+PRP in durvalumab-treated patients were investigated using univariate and multivariate logistic regression. PFS and OS were analyzed using Cox proportional hazards models adjusted for time-dependent G2+PRP plus covariates for randomization stratification factors without and with additional baseline factors. Results: On-study G2+PRP occurred in 94 of 475 (19.8%) and 33 of 234 patients (14.1%) on durvalumab and placebo, respectively (median follow-up, 25.2 mo); grade greater than or equal to 3 PRP was uncommon (4.6% and 4.7%, respectively). Time to onset and resolution of G2+PRP was similar with durvalumab and placebo. Univariate and multivariate analyses identified patients treated in Asia, those with stage IIIA disease, those with performance status of 1, and those who had not received induction chemotherapy as having a higher risk of G2+PRP. PFS and OS benefit favoring durvalumab versus placebo was maintained regardless of time-dependent G2+PRP. Conclusions: Factors associated with higher risk of G2+PRP with durvalumab after cCRT were identified. Clinical benefit was maintained regardless of on-study G2+PRP, suggesting the risk of this event should not deter the use of durvalumab in eligible patients with unresectable stage III NSCLC.

Published in JTO Clinical and Research Reports

ISSN: 2666-3643 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Website: https://www.journals.elsevier.com/jto-clinical-and-research-reports/

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