FDA Approves Drug for Patients With Solid Tumors and NTRK Gene Fusions

The FDA has granted accelerated approval to larotrectinib (Vitrakvi; Loxo Oncology and Bayer) for the treatment of adult and pediatric patients with solid tumors that have an NTRK gene fusion without a known resistance mutation. This approved indication applies to patients with disease that is metastatic or unresectable, as well as patients who have no suitable alternative treatments.

"Today’s approval marks another step in an important shift toward treating cancers based on their tumor genetics rather than their site of origin in the body," said Scott Gottlieb, MD, FDA Commissioner, in a press release.

Larotrectinib marks the first drug approved for NTRK gene fusion–positive cancers, and the second FDA approval of a tissue-agnostic treatment for cancer. The therapy was approved under the FDA’s priority review process and was given breakthrough therapy and orphan drug designation.

The approval for larotrectinib was based on efficacy data from the first 55 patients with unresectable or metastatic solid tumors with an NTRK gene fusion enrolled in 3 clinical trials—LOXO-TRK-14001, SCOUT, and NAVIGATE. A total of 12 cancer types were represented, with the most common being salivary gland tumors (22%), soft-tissue sarcoma (20%), infantile fibrosarcoma (13%), and thyroid cancer (9%).

Positive NTRK gene fusion status was identified in local laboratories using next-generation sequencing or fluorescence in situ hybridization. The major efficacy measures were overall response rate (ORR) and duration of response.

The ORR was 75%, including 22% complete responses and 53% partial responses. The duration of response was ≥6 months for 73% of patients, ≥9 months for 63%, and ≥12 months for 39%; as of the time of data cutoff, the median response duration had not been reached.

The most common adverse events with larotrectinib were fatigue, nausea, dizziness, vomiting, increased aspartate transaminase, cough, increased alanine transaminase, constipation, and diarrhea.—Janelle Bradley