Simultaneous Durvalumab and Platinum-Based Chemoradiotherapy in Unresectable Stage III Non–Small Cell Lung Cancer: The Phase III PACIFIC-2 Study
Abstract
PURPOSE Immunotherapy targeting PD-L1 improves outcomes in patients with unresectable stage III non–small cell lung cancer (NSCLC) and no progression after definitive, concurrent chemoradiotherapy (cCRT). Earlier administration of immunotherapy, simultaneously with cCRT, may improve outcomes further. METHODS Eligible patients were randomly assigned (2:1) to receive either durvalumab or placebo administered from the start of cCRT. Patients without progression after completing cCRT received consolidation durvalumab or placebo (per initial random assignment) until progression. The primary end point was progression-free survival (PFS) by blinded independent central review. Key secondary end points included objective response rate (ORR), overall survival (OS), the proportion of patients alive at 24 months (OS24), and safety. RESULTS In total, 328 patients were randomly assigned to receive durvalumab (n = 219) or placebo (n = 109). There was no statistically significant difference with durvalumab versus placebo in PFS (hazard ratio [HR], 0.85 [95% CI, 0.65 to 1.12]; P = .247) or OS (HR, 1.03 [95% CI, 0.78 to 1.39]; P = .823); OS24 was 58.4% versus 59.5%, respectively. Confirmed ORR was 60.7% with durvalumab versus 60.6% with placebo (difference, 0.2% [95% CI, −15.2 to 16.3%]; P = .976). With durvalumab versus placebo, respectively, maximum grade 3 or 4 adverse events (AEs) occurred in 53.4% versus 59.3% of patients, pneumonitis or radiation pneumonitis (group term) in 28.8% (grade ≥3: 4.6%) versus 28.7% (grade ≥3: 5.6%), AEs leading to discontinuation of durvalumab or placebo in 25.6% versus 12.0%, and fatal AEs in 13.7% versus 10.2%. CONCLUSION Among patients with unresectable stage III NSCLC, durvalumab administered from the start of cCRT failed to demonstrate additional benefit compared with cCRT plus placebo. Consolidation durvalumab following definitive cCRT remains the standard of care in this setting.
Article Details
Journal Info
Journal of Clinical Oncology
Lippincott Williams & Wilkins
Authors (102)
Jeffrey D. Bradley
Hospital of the University of Pennsylvania Radiation Oncology, Philadelphia, PA
Ana Caroline Zimmer Gelatti
Centro de Pesquisa em Oncologia (CPO) do Hospital São Lucas da PUCRS, Porto Alegre, Brazil and Grupo Brasileiro Oncologia Torácica (GBOT), Porto Alegre, Brazil
Juliana Janoski de Menezes
Michael Newton
Pratibha Chander
Nan Jia
Zofia F. Bielecka
Gustavo Girotto
Fernanda Peria
Gustavo Pinto
Pedro Marchi
Eduardo Silva
Ana Gelatti
Gilberto de Castro
Instituto do Cancer do Estado de São Paulo, São Paulo
Sérgio de Azevedo
Adilson Faccio
Yeni Neron
Oncology Research Center, Florianopolis, Brazil
Thais Almeida
Juliana de Menezes
Milada Zemanova
Ondrej Bilek
Jaromir Roubec
Hospital AGEL Ostrava – Vitkovice, Ostrava, Czech Republic
Gyula Ostoros
Zsuzsanna Szalai
Ibolya Laczó
Andrea Fülöp
György Losonczy
Gabriella Galffy
Hari Goyal
Nirav Asarawala
Satheesh Thungappa
Rajeev L. Krishnappa
Sewanti Limaye
Sankar Srinivasan
Apollo Speciality Hospital, Chennai, India
Mohamed Sehran
Sushant Mittal
Kartikeya Jain
Shailesh Bondarde
Apex Wellness Hospital, Nashik, India
Isamu Okamoto
Hidetoshi Hayashi
Young Hak Kim
Yuichi Sakamori
Kaoru Kubota
Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan
Shunichi Sugawara
Department of Pulmonary Medicine, Sendai Kousei Hospital, Sendai, Japan
Makoto Nishio
The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
Toyoaki Hida
Teppei Yamaguchi
Aichi Cancer Center, Nagoya, Japan
Tetsuro Kondo
Juan Vazquez Limón
Froylan López-López
Jorge Alatorre Alexander
Alejandro Molina Alavez
Manuel Magallanes Maciel
Jose Gomez Rangel
Manuel Leiva
Henry Gomez
Natalia Valdiviezo
Department of Oncology, Instituto Nacional de Enfermedades Neoplasicas, Lima, Peru
Paolo Valdez
Vanessa Bermudez
Alejandro Figueroa
Jerry Tan Chun Bing
Marie Grace Dawn Isidro
Cherry Pink Villa
Barbara Domingo
Teresa Sy Ortin
Annielyn Beryl Cornel
Joseph Parra
Rafał Dziadziuszko
Dariusz Kowalski
Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie Państwowy Instytut Badawczy, Klinika Nowotworow Pluca i Klatki Piersiowej, Warsaw, Poland
Bogdan Zurawski
Department of Outpatient Chemotherapy, Professor Franciszek Lukaszczyk Oncology Center, Bydgoszcz, Poland
Andrzej Badzio
Ewa Wasilewska-Teśluk
Konstantin Laktionov
Galina Statsenko
Mikhail Dvorkin
Evgeniy Levchenko
Ekaterina Solovyeva
Lyubov Vladimirova
Alexander Arkhipov
Natalia Fadeeva
Valery Breder
Dong-Wan Kim
School of Civil, Environmental and Architectural Engineering, Korea University, Seoul 02841, Republic of Korea
Sang-We Kim
Asan Medical Center, Seoul, South Korea
Keunchil Park
Ki Hyeong Lee
Chungbuk National University Hospital, Cheongju-si, North Chungcheong, Cheongju, South Korea
Sung Sook Lee
Gyeong-Won Lee
4Institute of Health Science, Gyeongsang National University Hospital, Gyeongsang National University College of Medicine, Jinju, Korea
Virote Sriuranpong
Sarayut Geater
Busyamas Chewaskulyong
Jarin Chindaprasirt
Siriwimon Saichamchan
Ahmet Demirkazik
Hasan Coskun
Tuncay Goksel
Mustafa Erman
Mustafa Özgüroğlu
Muhammed Kaplan
Huyen Phung
Khoi Nguyen
Department of Biomedical Engineering and Institute for Quantitative Health Science and Engineering, Michigan State University
Anh Le
Dinh Tien Nguyen