ASCO discussant Nicole Chau, MD, Clinical Associate Professor at the University of British Columbia/BC Cancer in Vancouver, said the COSMIC-311 trial was “noteworthy for meeting its co-primary endpoint of progression-free survival (hazard ratio = 0.22) in this heavily pretreated patient population.”
She pointed out the difficulty of treating radioactive iodine–refractory differentiated thyroid cancer: “These patients have a poor prognosis. Two VEGFR multikinase inhibitors have been approved in the first-line setting, based on phase III trials demonstrating improved progression-free survival. Invariably, all patients will develop resistance; however, there are no standard second-line therapies,” she said.
“I congratulate the investigators for this study, which is the first global randomized phase III trial to evaluate cabozantinib in patients with radioactive iodine–refractory disease progressing during or after treatment with at least one VEGFR multikinase inhibitor,” stated Dr. Chau. The “impressive findings” prompted early stopping of the study.
Nicole Chau, MD
Noteworthy Data
“Of note, 63% of the patients had received prior lenvatinib, 37% had prior sorafenib, and 26% had two prior VEGFR inhibitors,” she emphasized. Benefit was seen in all key subgroups, including according to the number of prior treatments.
Although the co-primary endpoint of overall response rate did not meet statistical significance, Dr. Chau offered this comment: “I think the disease control rate of 60% is clinically meaningful in this heavily pretreated population and is in keeping with the tumoristatic effects of the drug.”
Despite the strong efficacy, Dr. Chau pointed out that VEGFR multikinase inhibitors are associated with “challenging” toxicity. Most patients in this study required dose modification (78%) or reduction (57%). Although few patients (5%) discontinued cabozantinib, this percentage may increase with longer follow-up and accumulating toxicities, she predicted.
Data on correlative genomic biomarkers, quality of life, and financial toxicity are still needed, acknowledged Dr. Chau. “Due to the high unmet clinical need, these exciting results from the interim analysis of COSMIC-311 support cabozantinib as a potential second- or third-line VEGFR tyrosine kinase inhibitor option,” she concluded.
DISCLOSURE: Dr. Chau has received honoraria from Bayer, Eisai, Merck, and Roche Canada; has served as a consultant or advisor to Bayer, Eisai, Lilly, Merck, and Roche; has received research funding from GlaxoSmithKline; and has received institutional research funding from Merck and Pfizer.
