604P - Cabozantinib versus placebo in patients with radioiodine-refractory differentiated thyroid cancer who progressed after prior VEGFR-targeted therapy: Outcomes from COSMIC-311 by BRAF status

Background

Tyrosine kinase inhibitors (TKIs) are standard of care for radioiodine-refractory differentiated thyroid cancer(RAIR-DTC). Cabozantinib (Cabo) is a TKI approved for RAIR-DTC in the US (patients [pts] aged ≥12 years who progressed after VEGFR-targeted therapy) and in the EU (adult pts who progressed after systemic therapy), based on significant progression-free survival (PFS) improvement vs placebo in the phase 3 COSMIC-311 study (NCT03690388). BRAF mutations are common in thyroid cancer, but limited data are available to inform treatment in BRAF-mutated RAIR-DTC. BRAF- and MEK-directed therapies are approved in the US for pts with BRAF-mutated solid tumors, but supportive studies in DTC are lacking. In this planned exploratory analysis of COSMIC-311, we evaluated the efficacy and safety of Cabo vs placebo by BRAF status.

Methods

Pts with RAIR-DTC previously treated with 1-2 VEGFR-targeted therapies (lenvatinib or sorafenib required) were randomized to Cabo 60 mg PO QD or placebo. Primary endpoints were PFS and objective response rate (ORR), both per RECIST v1.1 by blinded independent review. For this analysis, outcomes were evaluated by BRAF status (BRAF-V600E or -wild type [wt]).

Results

Of258 randomized pts, BRAF status (V600E or wt) was determined for 101 pts: 27 were BRAF-V600E (Cabo 17, placebo 10) and 74 were BRAF-wt (Cabo 44, placebo 30). The PFS benefit of Cabo vs placebo was maintained irrespective of BRAF status (Table). Safety data by BRAF status were consistent with the overall study population. Table: 604P

NE, not estimable

Conclusions

In this subgroup analysis, Cabo was associated with improved PFS vs placebo irrespective of BRAF-V600E or wt status. These data, together with the manageable safety profile, support Cabo as a treatment option for RAIR-DTC after prior VEGFR-targeted therapy, including in BRAF-V600E disease.

Clinical trial identification

NCT03690388.

Editorial acknowledgement

Writing and editorial assistance was provided by Alexus Rivas-John, PharmD (Fishawack Communications Inc., part of Fishawack Health, Conshohocken, PA, USA).

Legal entity responsible for the study

Exelixis, Inc.

Funding

This study was funded by Exelixis, Inc. (Alameda, CA).

Disclosure

M.S. Brose: Financial Interests, Institutional, Research Grant: Exelixis, Bayer, Loxo/Lilly, Kinnate; Financial Interests, Personal, Advisory Role: Exelixis, Bayer, Loxo/Lilly, Kinnate. B. Keam: Financial Interests, Institutional, Research Funding: Ono, AZ, MSD; Financial Interests, Personal, Advisory Role: Handok, NeoImmuneTec, Trialinformatics, ImmuneOncia; Financial Interests, Personal, Other, Honoraria: AZ, Merck, MSD, LG Chem, Bayer, Yuhan. B. Robinson: Financial Interests, Personal, Leadership Role: Mayne Pharma; Financial Interests, Personal, Stocks or ownership: Mayne Pharma; Financial Interests, Personal, Other, Honoraria: Eisai, Eli Lilly; Financial Interests, Personal, Advisory Role: Eisai, Eli Lilly; Financial Interests, Personal, Speaker’s Bureau: Eisai. S. Sherman: Financial Interests, Personal, Advisory Role: Eisai Medical Research, Eli Lily; Financial Interests, Personal, Advisory Board, Co-chair: MD Anderson Cancer Center Data Safety Monitoring Board. J.A. Krajewska: Financial Interests, Personal, Advisory Role: Exelixis, Ipsen, Loxo, Lilly; Financial Interests, Personal, Other, Honoraria: Exelixis, Lilly; Financial Interests, Personal, Other, Honoraria; subinvestigator in clinical trials: Sanofi-Genzyme ; Financial Interests, Personal, Other, Honoraria for lectures: Ipsen and Sanofi-Genzyme; Financial Interests, Personal, Other, Travel Accommodations/Expenses: Ipsen, Sanofi; Financial Interests, Personal, Proprietary Information, EPO 21460001.7-1111: Patent aplications; Financial Interests, Personal, Advisory Board: Exelixis, Ipsen, Lilly, Loxo. C. Lin: Financial Interests, Personal, Advisory Role: AbbVie, Blueprint Medicines, Boehringer Ingelheim, Bristol Myers Squibb, Merck KGaA, Novartis, PharmaEngine; Financial Interests, Personal, Other, Honoraria: Boehringer Ingelheim, Daiichi Sankyo, Eli Lilly, Roche, Novartis; Financial Interests, Personal, Other, Travel Accommodations/Expenses: BeiGene, Daiichi Sankyo, Eli Lilly, IMPACT; Financial Interests, Personal, Advisory Board: Bayer, Novartis, Seagen. F. Vaisman: Financial Interests, Institutional, Research Funding: Eli Lilly, Exelixis; Financial Interests, Personal, Advisory Role: Eli Lilly, Ipsen; Financial Interests, Personal, Other, Honoraria: Merck, Eli Lilly, Ipsen, Sanofi; Financial Interests, Personal, Other, Travel Accommodations/Expenses: Merck, Sanofi. A.O. Hoff: Financial Interests, Personal, Full or part-time Employment, Husband: Oncologia Rede D'OR; Financial Interests, Personal, Leadership Role, Husband - President: Oncology Rede D'OR; Financial Interests, Institutional, Research Funding: Exelixis, Eli Lilly; Financial Interests, Personal, Advisory Role: Eli Lilly; Financial Interests, Personal, Other, Honoraria: Bayer; Financial Interests, Personal, Advisory Board: Eli Lilly. D.W. Bowles: Financial Interests, Institutional, Research Funding: Pfizer, Exelixis; Financial Interests, Personal, Advisory Role: Exelixis. N. Ngamphaiboon: Financial Interests, Personal, Advisory Role: MSD, Roche, Eisai, Merck, BeiGene, BMS; Financial Interests, Institutional, Research Funding: MSD, Roche, RAPT therapeutics, BeiGene, Boehringer Ingelheim Pharmaceuticals, Pfizer, Exelixis; Financial Interests, Personal, Other, Honoraria: Roche, MSD, Merck, Eisai; Financial Interests, Personal, Other, Travel Accommodations/Expenses: Roche, MSD, Eisai; Financial Interests, Personal, Advisory Board: MSD, Roche, Eisai, Merck, BeiGene, BMS, Boehringer Ingelheim. X. Guo: Financial Interests, Personal, Full or part-time Employment: Exelixis; Financial Interests, Personal, Other, Methods for selecting psoriatic arthritis subjects for treatment with a TYK2 inhibitor based on blood protein biomarker levels. (US Patent Application No. 029420.4032 - Oct 19 2021.): Patent application; Financial Interests, Personal, Stocks/Shares: Exelixis, AstraZeneca, Pfizer, AbbVie. F. Zhang, D.S. Williamson, D. Curran, N. Berry: Financial Interests, Personal, Full or part-time Employment: Exelixis, Inc.; Financial Interests, Personal, Stocks/Shares: Exelixis, Inc. M. Schwickart: Financial Interests, Personal, Full or part-time Employment: Exelixis, Inc.; Financial Interests, Personal, Stocks/Shares: Exelixis, Inc., Revolution medicine. J. Capdevila Castillon: Financial Interests, Institutional, Research Funding: Novartis, Pfizer, AstraZeneca, Advanced Accelerator Applications, Eisai, Amgen, Bayer; Financial Interests, Personal, Advisory Role: Novartis, Pfizer, Ipsen, Exelixis, Bayer, Eisai, dvanced Accelerator Applications, Amgen, Sanofi, Lilly, Huchinson Pharma, ITM, Advanz, Merck Serono, Esteve, Roche. All other authors have declared no conflicts of interest.