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.
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, MD19 for the POSEIDON investigators
Source: DOI: 10.1200/JCO.22.00975 Journal of Clinical Oncology
Dr. Anjan Patel's Thoughts
Suddenly met-NSCLC is a crowded space. This study did not conclude that T+D+CT was better than D+CT. The findings showed that D+CT was better than CT alone. The addition of T to D+CT improved the PFS and OS trend, but I don’t think this was a home run result. There was no significant OS benefit, and further follow-up will declare these results. Also, improved outcomes were not seen in the non-squamous population. The pembrolizumab studies have 5+ years of follow-up and an improvement in PFS and OS across NSCLC subtypes.
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, ChinaRelated Articles
Burden of chemotherapy-induced myelosuppression among patients with extensive-stage small cell lung cancer: A retrospective study from community oncology practices
FCS medical oncologist and hematologist Lowell L. Hart, MD, FACP was first-author a study with FCS co-authors President and Managing Physician Lucio N. Gordan, MD, Director of Pharmacy Operations Kristen Boykin, Senior Vice President & Data Officer Trevor Heritage, PhD, and (Retired) Vice President of Pharmacy Services Ray Bailey BPharm, RPh, that evaluated ES-SCLC patients with chemotherapy-induced myelosuppression over a seven-year period, from January 2013 through December 2020. Within this cohort, 98% of the patients experienced at least one myelosuppressive episode following chemotherapy treatment, leading to the need for supportive care, creating additional costs in health care management and time lost in treatment for ES-SCLC.
Lung Cancer Diagnosed Through Screening, Lung Nodule, and Neither Program: A Prospective Observational Study of the Detecting Early Lung Cancer (DELUGE) in the Mississippi Delta Cohort
Interesting study which the demonstrates the importance of prescriptive approach to detect NSCLC. Hopefully, in the future ctDNA may enhance or replace LDCT ability to detect patients with stage I/II disease.
Neoadjuvant Nivolumab plus Chemotherapy in Resectable Lung Cancer
This is a potential practice-changing study. Future data on overall-survival (OS) will be important to confirm results. Patient selection will also evolve over time especially in real-world practice. I presume more patients with stage II/III will get neoadjuvant therapy as opposed to a patient with a small lung nodule (stage I) taken to surgery, unless if there is significant OS for early stage patients as well.
Rates of Guideline-Concordant Surgery and Adjuvant Chemotherapy Among Patients With Early-Stage Lung Cancer in the US ALCHEMIST Study (Alliance A151216)
Lots of progress to be accomplished here. Increased standardization of care, quality metrics based on guideline-adherence and best practices remain critical to progress.
