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, MD19 for 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, TN;
2Yonsei Cancer Center, Seoul, South Korea;
3Leningrad Regional Clinical Hospital, St Petersburg, Russia;
4Health Pharma Professional Research, Mexico City, Mexico;
5Prince of Songkla University, Songkhla, Thailand;
6Federal 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, Russia;
7Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea;
8Acinus, Kropyvnytskyi, Ukraine;
9Florida Cancer Specialists—Sarah Cannon Research Institute, Leesburg, FL;
10Queen Mary University of London, London, United Kingdom;
11Chang Gung Memorial Hospital, Taoyuan City, Taiwan;
12Instituto Nacional de Cancer-INCA, Rio de Janeiro, Brazil;
13Kanagawa Cancer Center, Yokohama, Japan;
14Asklepios Lung Clinic, member of the German Center for Lung Research (DZL), Munich-Gauting, Germany;
15AstraZeneca, Gaithersburg, MD;
16AstraZeneca, Cambridge, United Kingdom;
17Centre Hospitalier Universitaire Vaudois, Lausanne University, Lausanne, Switzerland;
18David Geffen School of Medicine at UCLA, Los Angeles, CA;
19State Key Laboratory of Translational Oncology, Department of Clinical Oncology, Chinese University of Hong Kong, Hong Kong, China
