Clinical trial results of RET kinase inhibitor selpercatinib show that the targeted therapy was effective in preventing or inhibiting the growth of tumours in RET fusion-positive cancers other than lung and thyroid cancers.

The results, derived from a cohort of patients enrolled in the phase 1/2 LIBRETTO-001 trial, were presented at the virtual AACR Annual Meeting 2021 by Vivek Subbiah, M.D., associate professor of Investigational Cancer Therapeutics.

Selpercatinib became the first treatment approved by the Food and Drug Administration (FDA) to treat RET fusion-positive lung and thyroid cancers, as well as RET-mutant medullary thyroid cancer (MTC), in May 2020.

However, because RET alterations also have been shown to be oncogenic drivers in the pathogenesis of other cancers, it was postulated that selpercatinib could be used to treat other advanced solid tumours in which RET alterations occur.

"Selpercatinib demonstrates promising activity across a variety of non-lung and non-thyroid RET fusion-positive advanced solid tumours, including treatment-refractory GI malignancies," Subbiah said. "Although RET fusions are rare, this undoubtedly has conferred clinical benefit and the gift of time to these patients."

Thirty-two patients with RET fusion-positive non-lung or non-thyroid cancers participated in the study, representing 12 unique tumour types -- including pancreatic, colon, breast, salivary, sarcoma and pulmonary carcinosarcoma.

Twenty-nine of the patients were previously treated with systemic therapy.

The objective response rate in this heavily pretreated patient population was 47%, including complete responses observed in two patients.

Responses were observed across nine unique cancer types and a spectrum of fusion partners.

Responses were ongoing in 73% of the patients, and the median duration of response was not reached at a follow-up of 13 months.

The safety profile of this cohort is consistent with the known profile of selpercatinib in the overall LIBRETTO-001 population.

The LIBRETTO-001 trial, which spans 16 countries and 89 sites, continues to enrol patients with RET-altered non-lung cancer.

"These are definitely impactful data for precision oncology from the clinical and translational perspective," Subbiah emphasised. "These analyses reiterate the importance of broad-based genomic profiling to identify actionable oncogenic drivers, including RET fusions."

Source: University of Texas MD Anderson Cancer Center