ECE2022 Oral Communications Oral Communications 3: Thyroid 1 (6 abstracts)
Cabozantinib versus placebo in patients with radioiodine-refractory differentiated thyroid cancer (DTC) who have progressed after prior VEGFR-Targeted yherapy: updated results from the phase 3 COSMIC-311 trial and prespecified subgroup analyses based on prior therapy
Cosimo Durante 1 , Marcia Brose 2,3 , Bruce Robinson 4 , Steven I Sherman 5 , Barbara Jarzab 6 , Chia-Chi Lin 7 , Fernanda Vaisman 8 , Ana O Hoff 9 , Erika Hitre 10 , Daniel W Bowles 11 , Suvajit Sen 12 , Purvi Patel 12 , Bhumsuk Keam 13 & Jaume Capdevila 14
1Sapienza University of Rome, Department of Translational and Precision Medicine, Roma, Italy; 2University of Pennsylvania, Abramson Cancer Center, Philadelphia, United States; 3Thomas Jefferson University Medical School, Sidney Kimmel Cancer Center, Philadelphia, Pennsylvania, United States; 4The University of Sydney, Sydney Medical School, Sydney, New South Wales, Australia; 5The University of Texas MD Anderson Cancer Center, Department of Endocrine Neoplasia and Hormonal Disorders, Houston, United States; 6M. Sklodowska-Curie National Research Institute of Oncology, Gliwie Branch, Poland; 7National Taiwan University Hospital, Department of Oncology, Taiwan; 8The National Cancer Institute, Rio de Janeiro, Mexico; 9University of São Paulo, Department of Endocrinology, Instituto do Câncer do Estado de São Paulo, Brazil; 10National Institute of Oncology, Department of Medical Oncology and Clinical Pharmacology “B,”, Budapest, Hungary; 11University of Colorado Anschutz Medical Campus, Division of Medical Oncology, Department of Medicine, Aurora, United States; 12Exelixis Inc, Alameda, California, United States; 13Seoul National University Hospital, Seoul, Rep. of South Korea; 14VHIO Vall d’Hebron Institut d’Oncologia, Barcelona, Spain
Background: At a preplanned interim analysis (median follow-up 6.2 months) of the double-blind, phase 3 COSMIC-311 trial (NCT03690388), cabozantinib significantly improved progression-free survival (PFS) vs placebo (HR 0.22, 96% CI 0.13-0.36; P<0.0001) in 187 patients with previously treated radioiodine-refractory DTC (Brose, Lancet Oncol; 2021). Patients must have received lenvatinib or sorafenib and progressed during or after 1-2 prior VEGFR inhibitors. We present the final analysis with an extended datacut of all randomized patients (ITT population) and for prespecified subgroups who received prior lenvatinib, sorafenib, or both.
Methods: Patients were randomized 2:1 to cabozantinib (60 mg QD) or placebo. Placebo patients could cross over to open-label cabozantinib upon disease progression per blinded independent radiology committee (BIRC). PFS (ITT) and objective response rate (ORR, first 100 randomized patients) per RECIST v1.1 by BIRC were the primary endpoints.
Results: At final analysis 258 patients (170 cabozantinib, 88 placebo) were randomized at data cut (8 Feb 2021); 96 had received prior sorafenib/no lenvatinib, 102 prior lenvatinib/no sorafenib, and 60 prior sorafenib and lenvatinib. Median follow-up was 10.1 months. Forty patients crossed over to receive cabozantinib. Median PFS was 11 months for cabozantinib vs 1.9 months for placebo in the ITT population (HR=0.22, 95% CI 0.15-0.31; P<0.0001). For subgroups, median PFS was 16.6 vs 3.2 months for prior sorafenib/no lenvatinib (HR=0.13, 95% CI 0.06-0.26); 5.8 vs 1.9 months for prior lenvatinib/no sorafenib (HR=0.28, 95% CI 0.17-0.48), and 7.6 vs 1.9 months for prior sorafenib and lenvatinib (HR=0.27, 95% CI 0.13-0.54). In the ITT population, ORR was 11% for cabozantinib vs 0% for placebo & overall survival HR=0.76 (95% CI 0.45-1.31). Grade 3/4 treatment emergent adverse events (TEAEs) were 62% in the cabozantinib arm vs 28% in placebo with no treatment-related grade 5 events; 67% vs 5% required dose reductions due to TEAEs; 8.8% vs 0% discontinued treatment due to TEAEs not causally related to disease.
Conclusion: In the final analysis of COSMIC-311 with longer follow-up, cabozantinib maintained its superior efficacy versus placebo. The PFS-HR was consistent with the interim analysis, in patients with previously treated radioiodine-refractory DTC irrespective of prior treatment, with no unexpected toxicities.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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