Cabozantinib approved in patients with radioiodine-refractory differentiated thyroid cancer who have progressed after prior VEGFR-targeted therapy: Updated results from the phase III COSMIC-311 trial
Although differentiated thyroid cancer (DTC) is usually curable with surgery, radioactive iodine (RAI), and thyroid-stimulating hormone (TSH) suppression, disease recurrence and/or distant metastases is less common with poor prognosis of patients. Cabometyx (Cabozantinib) recently got a USFDA approval for the second line treatment in adult and pediatric patients 12 years of age and older with locally advanced or metastatic DTC who are radioactive iodine-refractory or ineligible. The review and approval process was expedited on the basis of the final analysis of the phase III COSMIC-311 trial, which was presented during a mini oral session for NETs and endocrine tumors on the 3rd day of ESMO 2021. (LBA67)
The pivotal phase III trial, COSMIC-311, which was sponsored by Exelixis and co-funded by Ipsen, enrolled 258 patients who received either Cabometyx 60 mg or placebo once daily. The primary endpoints of the trial were progression-free survival (PFS) and overall response rate (ORR). The results showed that at a median follow-up of 10.1 months, the significant improvement in PFS with cabozantinib was maintained, with consistent benefit in subgroups based on prior treatment. Cabozantinib reduced the risk of disease progression or death versus placebo in the intent-to-treat (ITT) population. Median PFS as assessed by BIRC was 11.0 months for patients treated with cabozantinib compared with 1.9 months for patients treated with placebo. Subgroup analyses demonstrated that cabozantinib improved PFS versus placebo irrespective of prior exposure to lenvatinib and/or sorafenib. An updated analysis for the primary endpoint of objective response rate (ORR) as assessed by BIRC in the ITT population favored cabozantinib at 11%. Median overall survival (mOS), an additional endpoint, was 19.4 months for patients treated with cabozantinib and not estimable for patients treated with placebo. Rates of grade 3/4 treatment-emergent AEs were 62% for cabozantinib versus 28% for placebo, with no treatment-related deaths.
Expert opinion- “Given the urgent need for new treatments for differentiated thyroid cancer, I’m encouraged to see that cabozantinib benefited patients in COSMIC-311 both at a longer follow-up and across prior therapy subgroups. These strong findings, which formed the basis for the recent U.S. FDA approval, further support cabozantinib as an important new treatment option for patients with radioactive iodine-refractory differentiated thyroid cancer who previously had no standard of care following disease progression on anti-VEGFR therapy.”
- Expert Opinion
INSIGHTS- The application for cabozantinib was approved following the pre-set Prescription Drug User Fee Act (PDUFA) target action date of December 4, 2021. Prior the approval of the asset, patients with radioactive iodine-refractory differentiated thyroid cancer who had progressed following prior VEGFR-targeted therapy were facing aggressive disease with no standard treatment option. But this approval came as an important advancement for those patients who were in dire need of new treatment options. Delveinsight reckons that Exelixis’ cabozantinib has the potential to generate a significant market size in this indication. We also estimate its good earnings from the first-line advanced renal cell carcinoma market as it was recently approved in combination with nivolumab (Opdivo; BMS) in January 2021.