Single-Agent Divarasib (GDC-6036) in Solid Tumors with a KRAS G12C Mutation
Another KRAS G12C inhibitor. Congrats to FCS Director of Drug Development Manish Patel, MD, one of the authors. Durable responses with less adverse events.
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, ChinaRelated Articles
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Neoadjuvant chemotherapy trial with post op nivolumab for 6 months shows promising results.
First-line atezolizumab monotherapy versus single-agent chemotherapy in patients with non-small-cell lung cancer ineligible for treatment with a platinum-containing regimen (IPSOS): a phase 3, global, multicentre, open-label, randomised controlled study
Patients with poor performance status do better on atezolizumab monotherapy vs. single agent chemotherapy.
Phase II, Open-Label Study of Encorafenib Plus Binimetinib in Patients With BRAFV600-Mutant Metastatic Non–Small-Cell Lung Cancer
Targeted therapy in NSCLC, FCS was part of this trial.
Perioperative Nivolumab and Chemotherapy in Stage III Non–Small-Cell Lung Cancer
The NADIM-II study looked at perioperative Nivo+chemo vs. chemo alone in stIIIA – stIIIB NSCLC. High pCR rates with chemoIO are again seen, as in the Checkmate 816 and NADIM-I study, they were even higher in this cohort (37%), suggesting higher-stage patients derive the biggest benefit from neoadjuvant chemoIO. Pretty impressive results, however, I still must point out that this was a phase II study with a small sample size, OS benefits have not been demonstrated and this has yet to make it on to NCCN.
