Simultaneous Durvalumab and Platinum-Based Chemoradiotherapy in Unresectable Stage III Non–Small Cell Lung Cancer: The Phase III PACIFIC-2 Study
Jeffrey D. Bradley, Shunichi Sugawara, Ki Hyeong Lee, Gyula Ostoros, Ahmet Demirkazik, Milada Zemanová, Virote Sriuranpong, Ana Caroline Zimmer Gelatti, J. Menezes, Bogdan Żurawski, Michael Newton, Pratibha Chander, Nan Jia, Zofia F. Bielecka, Mustafa Özgüroğlu, on behalf of the PACIFIC-2 Investigators, Gustavo Girotto, Fernanda Maris Peria, Gustavo Sanches Faria Pinto, Pedro De Marchi, Eduardo Silva, Ana Caroline Zimmer Gelatti, Gilberto de Castro, Sérgio de Azevedo, Adilson Faccio, Yeni Nerón, Thaís Gomes de Almeida, Juliana de Menezes, Milada Zemanová, Ondřej Bílek, Jaromı́r Roubec, Gyula Ostoros, Zsuzsanna Szalai, Ibolya Laczó, Andrea Fülöp, György Losonczy, Gabriella Gálffy, Hari Om Goyal, Nirav Asarawala, Satheesh Chiradoni Thungappa, R Krishnappa, Sewanti Limaye, Sankar Srinivasan, Mohamed Sehran, Sushant Mittal, Kartikeya Jain, Shailesh Bondarde, Isamu Okamoto, Hidetoshi Hayashi, Young Hak Kim, Yuichi Sakamori, Kaoru Kubota, Shunichi Sugawara, Makoto Nishio, Toyoaki Hida, Teppei Yamaguchi, Tetsuro Kondo, Juan Vazquez Limón, Froylán López-López, J.A. Alatorre Alexander, Alejandro Molina Alavez, Manuel Magallanes Maciel, J. Gomez Rangel, Manuel Leiva, Henry Gómez, Natalia Valdiviezo, Paolo Valdez, Vanessa Bermudez, Alejandro Figueroa, Jerry Tan Chun Bing, Marie Grace Dawn Isidro, Cherry Pink Villa, Barbara Domingo, Teresa T. Sy Ortin, Annielyn Beryl Cornel, Joseph Parra, Rafał Dziadziuszko, Dariusz M. Kowalski, Bogdan Żurawski, A. Badzio, Ewa Wasilewska-Teśluk, К. К. Лактионов, Galina Statsenko, Mikhail Dvorkin, Evgeniy Levchenko, Ekaterina Solovyeva, Lyubov Vladimirova, Alexander Arkhipov, Natalia Fadeeva, Valery Breder, Dong‐Wan Kim, Sang‐We Kim, Keunchil Park, Ki Hyeong Lee, Sung Sook Lee, Gyeong‐Won Lee, Virote Sriuranpong, Sarayut Lucien Geater, Busyamas Chewaskulyong, Jarin Chindaprasirt
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.