ASCO Oral: Phase III COSMIC-311 promises a new standard of care for patients with previously treated differentiated thyroid cancer

Dr. Jaume Capdevila
  • Selected as an Oral Presentation during the American Society of Clinical Oncology (ASCO) 2021 Virtual Annual Meeting, 04 – 08 June, results from the global phase III COSMIC-311 trial show promise for patients with radioiodine-differentiated thyroid cancer (DTC) whose disease progressed on prior VEGFR-targeted therapies.
  • Stepping up as a new treatment option for these patients, for whom there is no other standard of care, single-agent cabozantinib (Cabometyx®) demonstrates a clinical and statistical improvement in progression-free survival (PFS) over placebo, with no unexpected toxicities.
  • Based on encouraging results from previous phase I and II studies, COSMIC-311 is an ongoing, multicenter, randomized, double-blind and placebo-controlled study designed to validate the clinical benefits of the cabozantinib multikinase inhibitor in this patient population.

Barcelona, June 07, 2021-  Thyroid cancer is responsible for 586,000 cases worldwide, ranking in 9th place for incidence in 2020 (1). Differentiated thyroid tumors, which make up about 90 percent of all thyroid cancers, are usually treated with surgery followed by ablation of the remaining thyroid with radioiodine. Around 5 – 15 percent of these tumors are resistant to radioiodine therapy.

Representing an unmet clinical need, patients with radioiodine-refractory differentiated thyroid cancer (DTC) whose disease has progressed after up to two prior vascular endothelial growth factor receptor (VEGFR)-targeted therapies, have no other standard of care treatment opportunities.

Based on encouraging results from previous phase I and II clinical studies, the COSMIC-311 phase III trial (NCT03690388) evaluated the efficacy and safety of cabozantinib versus placebo to assess its potential in improving outcomes for patients suffering from this intractable form of thyroid cancer. This pivotal, international trial, directed by Principal Investigator Marcia S. Brose, Director of the Center for Rare Cancers and Personalized, Abramson Cancer Center, University of Pennsylvania (PA, USA), has enrolled a total of 300 patients across 150 sites, including the Vall d’Hebron Institute of Oncology –VHIO (Vall d’Hebron Barcelona Hospital Campus, Spain).

 Co-led by Jaume Capdevila, Medical Oncologist and Clinical Investigator of VHIO’s Gastrointestinal & Endocrine Tumors Group (PI: Teresa Macarulla, Director: Josep Tabernero), alongside many other renowned experts in thyroid cancer, COSMIC-311 randomized patients in a 2:1 ratio to receive either cabozantinib or placebo, stratified by prior lenvatinib treatment and age (65 years of age or less), who had progressed during/after treatment with up to 2 prior VEGFR-target therapies.

 Presented during an Oral Abstract Session at the American Society of Clinical Oncology (ASCO), 2021 Virtual Annual Meeting, 04 – 08 June, interim results revealed data from the first 187 patients to participate in the trial (2).

“Achieving the primary endpoint of progression-free survival (PFS), in all randomized patients including those who had previously received lenvatinib, cabozantinib showed clinical and statistical improvements in PFS over placebo, with no unexpected toxicities,” noted Jaume Capdevila.

These results show promise for the more effective treatment of these patients, particularly considering that the average life expectancy is estimated at around three to six years from the time that metastatic disease is detected.

Crucially, patients responding to cabozantinib currently have no other standard of care options. Cabozantinib is the first multikinase inhibitor to show significant clinical benefit in this patient population whose disease has progressed on sorafenib and lenvatinib. This study consequently signposts a new standard of care to significantly increase survival for our patients,” he concluded.


  1. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021 May;71(3):209-249.
  2. Marcia S. Brose, Bruce Robinson, Steven I. Sherman, Barbara Jarzab, Chia-Chi Lin, Fernanda Vaisman, Ana Hoff, Erika Hitre, Daniel W. Bowles, Leonardo Faoro, Kamalika Banerjee, Jennifer W. Oliver, Bhumsuk Keam, Jaume Capdevila. Cabozantinib versus placebo in patients with radioiodine-refractory differentiated thyroid cancer who have progressed after prior VEGFR-targeted therapy: results from the phase 3 COSMIC-311 trial. ASCO 2021.



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