Author(s): Melissa L. Johnson, MD1; Byoung Chul Cho, MD, PhD2; Alexander Luft, MD3; Jorge Alatorre-Alexander, MD4; Sarayut Lucien Geater, MD5; Konstantin Laktionov, MD6; Sang-We Kim, MD, PhD7; Grygorii Ursol, MD8; Maen Hussein, MD9; Farah Louise Lim, MBBS, MRCP10; Cheng-Ta Yang, MD11; Luiz Henrique Araujo, MD, PhD12; Haruhiro Saito, MD, PhD13; Niels Reinmuth, MD, PhD14; Xiaojin Shi, MD15; Lynne Poole, MSc16; Solange Peters, MD, PhD17; Edward B. Garon, MD18; and Tony Mok, MD19for the POSEIDON investigators
PURPOSE
The open-label, phase III POSEIDON study evaluated tremelimumab plus durvalumab and chemotherapy (T + D + CT) and durvalumab plus chemotherapy (D + CT) versus chemotherapy alone (CT) in first-line metastatic non–small-cell lung cancer (mNSCLC).
METHODS
Patients (n = 1,013) with EGFR/ALK wild-type mNSCLC were randomly assigned (1:1:1) to tremelimumab 75 mg plus durvalumab 1,500 mg and platinum-based chemotherapy for up to four 21-day cycles, followed by durvalumab once every 4 weeks until progression and one additional tremelimumab dose; durvalumab plus chemotherapy for up to four 21-day cycles, followed by durvalumab once every 4 weeks until progression; or chemotherapy for up to six 21-day cycles (with or without maintenance pemetrexed; all arms). Primary end points were progression-free survival (PFS) and overall survival (OS) for D + CT versus CT. Key alpha-controlled secondary end points were PFS and OS for T + D + CT versus CT.
RESULTS
PFS was significantly improved with D + CT versus CT (hazard ratio [HR], 0.74; 95% CI, 0.62 to 0.89; P = .0009; median, 5.5 v 4.8 months); a trend for improved OS did not reach statistical significance (HR, 0.86; 95% CI, 0.72 to 1.02; P = .0758; median, 13.3 v 11.7 months; 24-month OS, 29.6% v 22.1%). PFS (HR, 0.72; 95% CI, 0.60 to 0.86; P = .0003; median, 6.2 v 4.8 months) and OS (HR, 0.77; 95% CI, 0.65 to 0.92; P = .0030; median, 14.0 v 11.7 months; 24-month OS, 32.9% v 22.1%) were significantly improved with T + D + CT versus CT. Treatment-related adverse events were maximum grade 3/4 in 51.8%, 44.6%, and 44.4% of patients receiving T + D + CT, D + CT, and CT, respectively; 15.5%, 14.1%, and 9.9%, respectively, discontinued treatment because of treatment-related adverse events.
CONCLUSION
D + CT significantly improved PFS versus CT. A limited course of tremelimumab added to durvalumab and chemotherapy significantly improved OS and PFS versus CT, without meaningful additional tolerability burden, representing a potential new option in first-line mNSCLC.
Author Affiliations
1Sarah Cannon Research Institute, Tennessee Oncology, PLLC, Nashville, TN2Yonsei Cancer Center, Seoul, South Korea3Leningrad Regional Clinical Hospital, St Petersburg, Russia4Health Pharma Professional Research, Mexico City, Mexico5Prince of Songkla University, Songkhla, Thailand6Federal State Budgetary Institution “N.N. Blokhin National Medical Research Center of Oncology” of the Ministry of Health of the Russian Federation (N.N. Blokhin NMRCO), Moscow, Russia7Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea8Acinus, Kropyvnytskyi, Ukraine9Florida Cancer Specialists—Sarah Cannon Research Institute, Leesburg, FL10Queen Mary University of London, London, United Kingdom11Chang Gung Memorial Hospital, Taoyuan City, Taiwan12Instituto Nacional de Cancer-INCA, Rio de Janeiro, Brazil13Kanagawa Cancer Center, Yokohama, Japan14Asklepios Lung Clinic, member of the German Center for Lung Research (DZL), Munich-Gauting, Germany15AstraZeneca, Gaithersburg, MD16AstraZeneca, Cambridge, United Kingdom17Centre Hospitalier Universitaire Vaudois, Lausanne University, Lausanne, Switzerland18David Geffen School of Medicine at UCLA, Los Angeles, CA19State Key Laboratory of Translational Oncology, Department of Clinical Oncology, Chinese University of Hong Kong, Hong Kong, China
