The Cancer Discovery research brief provides early but encouraging evidence that the sequential use of larotrectinib followed by LOXO-195 could extend the total duration of disease control for patients with TRK fusion cancers. An analogous paradigm has already been established for other oncogene-addicted tumors, such as those driven by androgen and estrogen signaling, EGFR mutations and ABL gene fusions. The brief describes the first two patients with TRK fusion cancers who responded to larotrectinib but later relapsed. An adult with colorectal cancer and a child with infantile fibrosarcoma were biopsied at the time of tumor progression and found to have a solvent front TRK mutation in the existing TRK fusion, which explained the diminished activity of larotrectinib. As no other treatment options exist to address TRK fusion solvent front mutations, Loxo Oncology, in collaboration with the U.S. FDA, enabled these patients to access LOXO-195 through emergency use Investigational New Drug applications (INDs). Both patients responded to LOXO-195, with minimal adverse events reported.
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