Cabozantinib May Be More Effective in Patients With Certain Mutations

Patients with medullary thyroid cancer who harbor RET M918T or RAS mutations may derive greater clinical benefit from cabozantinib compared with patients who do not have those genetic mutations, a study published in the journal Cancer has shown.1

A previously reported phase 3 trial demonstrated that cabozantinib significantly prolonged progression-free survival vs placebo in patients with progressive, metastatic medullary thyroid cancer. Researchers sought to conduct an exploratory analysis of that study to evaluate whether RET and RAS mutations impact the clinical activity of cabozantinib.

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Of the 330 patients enrolled, 51.2% were RET mutation-positive, 38.2% had a RET M918T mutation, 34.8% were RET mutation-unknown, 13.9% were RET mutation-negative, and 16 patients were RAS mutation-positive.

Results showed that cabozantinib appeared to prolong progression-free survival compared with placebo in the subgroups of patients who were RET mutation-positive (P <.0001), RET mutation-unknown (P =.0001), and RAS mutation-positive (P =.0317).

The investigators found that patients harboring the RET M918T mutation achieved the greatest observed progression-free survival benefit from cabozantinib therapy vs placebo (P <.0001).

Patients without RET or RAS mutations did not appear to derive a progression-free survival benefit from cabozantinib.

Despite these findings, a prospective trial is needed to confirm the association between these specific mutations and cabozantinib response in patients with medullary thyroid cancer.

Reference

1. Sherman SI, Clary DO, Elisei R, et al. Correlative analyses of RET and RAS mutations in a phase 3 trial of cabozantinib in patients with progressive, metastatic medullary thyroid cancer. Cancer. 2016 Aug 15. doi: 10.1002/cncr.30252. [Epub ahead of print]

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