Get a glimpse of pivotal abstracts from the ASCO21 presented in the Thyroid cancer space.
Abstract #6001: Ipsen and Exelixis’ phase III COSMIC-311 trial: Significant PFS benefit of Cabozantinib in previously treated radioiodine-refractory differentiated thyroid cancer
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. There is a high unmet need in radioiodine-refractory differentiated thyroid cancer (RAI-DTC) which had progressed after prior VEGFR-targeted therapy and currently, there is no established standard of care for this patient population.
Recently, at ASCO 2021 annual meeting, Exelixis stood out to present data from a phase III COSMIC-311 study that evaluated cabozantinib (arm 1) versus placebo (arm 2) in patients with RAI-DTC who had progressed after prior VEGFR-targeted therapy (lenvatinib or sorafenib). The primary endpoints were objective response rate (ORR) in the first 100 randomized patients and progression-free survival (PFS) in all randomized patients.
The study enrolled a total of 187 patients for the interim analysis with a data cut off of August 2020. The baseline characteristics of the study revealed that 63% of the patients in either of the arms had received prior therapy with lenvatinib. The efficacy analysis from the study revealed that the primary endpoint of median progression-free survival (mPFS) was met with the values of not reached (NR) for arm 1 and 1.9 months for arm 2. The mPFS hazard ratios (HR) of less than 1 among all the subgroups suggested that cabozantinib was a better treatment option than placebo. The ORR of 15% was observed in arm 1 over no ORR achieved in arm 2. The study results showed that the primary endpoint of ORR was not met. The disease control rate (DCR) of 60% was achieved in arm 1 over 27% in arm 2. At 6 months of minimum follow up, 76% of patients in arm 1 vs 29% patients in arm 2 experienced tumour reduction which was a significant value over placebo. The median overall (mOS) was not reached in either of the arms and a further follow up of the study is still required to attain the matured values. The safety analysis revealed that more than 50% of the patients in arm 1 and nearly 26% of patients in arm 2 experienced grade ≥3 adverse events (AEs).
Beneficial results from COSMIC-311 served as the basis for Exelixis’ recent NDA filing to the FDA. We believe that this would help in indicating the expansion of Cabozantinib. The above study results show that cabozantinib could be a new standard of care, if approved, however, the ORR value was not significantly different from placebo, the PFS values favored cabozantinib over placebo. The safety results were although higher with the experimental arm but were managed with supportive treatment therapies and dose modifications. If approved, RAI-DTC patients could rely their hope on cabozantinib without progression of the disease for a longer duration of time.
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