Tumor-agnostic therapy gets on TRK

Abstract

Cancer In precision oncology, treatment is tailored to match the specific mutations that drive tumor growth. To date, this targeted approach has emphasized highly recurrent mutations specific to certain tumor types—for example, the BRAF mutations that occur in about 40% of melanomas. This paradigm of tumor type–specific therapy is changing, however, with the recognition that diverse tumor types can share the same low-frequency mutations. Recent clinical work illustrates the promise of “tumor-agnostic” targeted therapy. Drilon et al. studied 55 patients with 17 distinct tumor types that harbored rare chromosomal fusions involving tropomyosin receptor kinase (TRK) genes. They found that larotrectinib, a TRK inhibitor, produced durable responses in about 70% of the patients, regardless of their tumor's tissue of origin. New Engl. J. Med. 378 , 731 (2018).