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Randomized Controlled Trial
. 2022 Dec 15;128(24):4203-4212.
doi: 10.1002/cncr.34493. Epub 2022 Oct 19.

Cabozantinib for previously treated radioiodine-refractory differentiated thyroid cancer: Updated results from the phase 3 COSMIC-311 trial

Marcia S Brose  1   2 , Bruce G Robinson  3 , Steven I Sherman  4 , Barbara Jarzab  5 , Chia-Chi Lin  6 , Fernanda Vaisman  7 , Ana O Hoff  8 , Erika Hitre  9 , Daniel W Bowles  10 , Suvajit Sen  11 , Jennifer W Oliver  11 , Kamalika Banerjee  11 , Bhumsuk Keam  12 , Jaume Capdevila  13
Affiliations
Randomized Controlled Trial

Cabozantinib for previously treated radioiodine-refractory differentiated thyroid cancer: Updated results from the phase 3 COSMIC-311 trial

Marcia S Brose et al. Cancer. .

Erratum in

Abstract

Background: At an interim analysis (median follow-up, 6.2 months; n = 187), the phase 3 COSMIC-311 trial met the primary end point of progression-free survival (PFS): cabozantinib improved PFS versus a placebo (median, not reached vs. 1.9 months; p < .0001) in patients with previously treated radioiodine-refractory differentiated thyroid cancer (RAIR-DTC). The results from an exploratory analysis using an extended datacut are presented.

Methods: Patients 16 years old or older with RAIR-DTC who progressed on prior lenvatinib and/or sorafenib were randomized 2:1 to oral cabozantinib tablets (60 mg/day) or a placebo. Placebo patients could cross over to open-label cabozantinib upon radiographic disease progression. The objective response rate (ORR) in the first 100 randomized patients and the PFS in the intent-to-treat population, both according to Response Evaluation Criteria in Solid Tumors version 1.1 by blinded, independent review, were the primary end points.

Results: At the data cutoff (February 8, 2021), 258 patients had been randomized (cabozantinib, n = 170; placebo, n = 88); the median follow-up was 10.1 months. The median PFS was 11.0 months (96% confidence interval [CI], 7.4-13.8 months) for cabozantinib and 1.9 months (96% CI, 1.9-3.7 months) for the placebo (hazard ratio, 0.22; 96% CI, 0.15-0.32; p < .0001). The ORR was 11.0% (95% CI, 6.9%-16.9%) versus 0% (95% CI, 0.0%-4.1%) (p = .0003) with one complete response with cabozantinib. Forty placebo patients crossed over to open-label cabozantinib. Grade 3/4 treatment-emergent adverse events occurred in 62% and 28% of the cabozantinib- and placebo-treated patients, respectively; the most common were hypertension (12% vs. 2%), palmar-plantar erythrodysesthesia (10% vs. 0%), and fatigue (9% vs. 0%). There were no grade 5 treatment-related events.

Conclusions: At extended follow-up, cabozantinib maintained superior efficacy over a placebo in patients with previously treated RAIR-DTC with no new safety signals.

Keywords: COSMIC-311; cabozantinib; differentiated thyroid cancer; phase 3; placebo; tyrosine kinase inhibitor.

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Conflict of interest statement

Marcia S. Brose has received honoraria from Bayer, Eisai, and Lilly; has a consulting or advisory role with Bayer, Blueprint Medicines, Eisai, Exelixis, Lilly, and Loxo; and has received institutional research funding from Bayer, Blueprint Medicines, Eisai, Exelixis, Lilly, and Loxo. Bruce G. Robinson has leadership roles with Cochlear and Mayne Pharma; has stock and other ownership interests in Cochlear and Mayne Pharma; has a consulting or advisory role with Eisai and Loxo; has participated in speakers’ bureaus with Eisai; and has received travel support, accommodations, or other expenses from Eisai. Steven I. Sherman has received honoraria from Eisai; has a consulting or advisory role with Exelixis, Lilly, and Loxo; and has received institutional research funding from Exelixis. Barbara Jarzab has received honoraria from Sanofi; has a consulting or advisory role with AstraZeneca, Ewopharma, and Ipsen; has participated in speakers’ bureaus with Exelixis; has acted as an independent contractor for Amgen, Eisai, Pfizer, Lilly, Sobi, and Oxigene; and has received travel support, accommodations, or other expenses from Edomed, Ipsen, Novartis, Bayer, Sobi, and Sanofi. Chia‐Chi Lin has received honoraria from Daiichi Sankyo, Lilly, Novartis, and Roche; has a consulting or advisory role with Blueprint Medicines, Boehringer Ingelheim, Daiichi Sankyo, and Novartis; has acted as an independent contractor for Bristol‐Myers Squibb, EMD Serono, BeiGene, and AbbVie; and has received travel support, accommodations, or other expenses from BeiGene, Daiichi Sankyo, Lilly, and Novartis. Fernanda Vaisman has a consulting or advisory role with Bayer HealthCare and Merck. Ana O. Hoff has received honoraria from Bayer (continuing medical education), Genzyme (continuing medical education), and United (continuing medical education); has a consulting or advisory role with Exelixis, Lilly, and Bayer; and has received institutional research funding from Exelixis and Lilly. Daniel W. Bowles has a consulting or advisory role with Exelixis. Suvajit Sen is an employee of Exelixis and has stock and other ownership interests with Exelixis. Jennifer W. Oliver is an employee of Exelixis and has stock and other ownership interests with Exelixis. Kamalika Mukherjee is an employee of Exelixis and has stock and other ownership interests with Exelixis. Bhumsuk Keam has received honoraria from AstraZeneca, Merck, and MSD Oncology; has a consulting or advisory role with ABL Bio, AstraZeneca, CbsBioscience, Cellid, Genexine, Handok, and MSD Oncology; and has received research funding from AstraZeneca, MSD Oncology, and Ono Pharmaceutical. Jaume Capdevila has a consulting or advisory role with Advanced Accelerator Applications, Bayer, Eisai, Exelixis, Ipsen, Lilly, Merck Serono, Novartis, Pfizer, Sanofi, and Vall Hebron; has participated in speakers’ bureaus with Bayer, Eisai, Ipsen, Lilly, Merck Serono, Novartis, Pfizer, and Sanofi; and has received institutional research funding from Advanced Accelerator Applications, AstraZeneca, Bayer, Eisai, Ipsen, Lilly, Novartis, and Pfizer. The other authors made no disclosures.

Figures

FIGURE 1
FIGURE 1
Patient disposition
FIGURE 2
FIGURE 2
Kaplan–Meier estimates of (A) PFS per RECIST v1.1 by a blinded independent radiology committee and (B) OS. CI indicates confidence interval; HR, hazard ratio; NE, not estimable; No., number; OS, overall survival; PFS, progression‐free survival; RECIST v1.1, Response Evaluation Criteria in Solid Tumors version 1.1
FIGURE 3
FIGURE 3
PFS in prespecified subgroups. aStratified hazard ratio. bThirty‐two patients with papillary differentiated thyroid cancer had a follicular variant. CI indicates confidence interval; ECOG, Eastern Cooperative Oncology Group; HR, hazard ratio; NE, not estimable; No., number; PFS, progression‐free survival; TKI, tyrosine kinase inhibitor; VEGFR, vascular endothelial growth factor receptor
See this image and copyright information in PMC

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