Durvalumab With or Without Tremelimumab in Combination With Chemotherapy as First-Line Therapy for Metastatic Non–Small-Cell Lung Cancer: The Phase III POSEIDON Study

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

Source: DOI: 10.1200/JCO.22.00975 Journal of Clinical Oncology 41, no. 6 (February 20, 2023) 1213-1227.

Dr. Maen Hussein's Thoughts

Another option for combination chemo immunotherapy; we have a clinical trial in FCS now with another combination of chemotherapy + PD-L1 and TIGIT inhibitors, PLEASE CONSIDER IT FOR UNRESECTABLE NSCLC patients.

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

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