Tissue-agnostic RET inhibition: can you trust your target?

Abstract

The field of oncology has changed vastly over the past two decades with the advent of immunotherapy and the expansion of targeted agents. The basket trial design has emerged as a means to evaluate novel treatments in a tissue-agnostic fashion. To date, tissue-agnostic approvals exist for anti-PD-1 antibodies in the setting of mismatch repair deficiency or high microsatellite instability or high tumour mutational burden, as well as TRK inhibitors for NTRK fusions and dabrafenib plus trametinib for BRAFV600E mutations (table). Approvals of several of these drugs were based on analyses of not only so-called anchor malignancies (those in which a given mutation is most prevalent), but also those belonging to the long tail, meaning cancer types less commonly associated with the alteration of interest. FDA=US Food and Drug Administration. EMA=European Medicines Agency. Tumour-agnostic efficacy and safety of selpercatinib in patients with RET fusion-positive solid tumours other than lung or thyroid tumours (LIBRETTO-001): a phase 1/2, open-label, basket trialSelpercatinib showed clinically meaningful activity in the RET fusion-positive tumour-agnostic population, with a safety profile consistent with that observed in other indications. Comprehensive genomic testing that includes RET fusions will be crucial for identifying patients who might benefit from selpercatinib. Full-Text PDF