WASHINGTON – The the oral agent larotrectinib (Vitrakvi) on Monday for treating metastatic or unresectable solid cancers of any type that harbor a neurotrophic receptor tyrosine kinase (NTRK) gene fusion, absent a known resistance mutation.
Based on pooled data from 55 adult and pediatric patients from three clinical trials, treatment with larotrectinib yielded an overall response rate of 75% (95% CI 61%-85%), with complete and partial responses in 22% and 53%, respectively. Median duration of response and progression-free survival had not been reached at the time of data analysis.
Responders included those with cancers of the lung, thyroid, colon, and salivary gland, as well as melanoma, soft-tissue sarcoma, infantile fibrosarcoma, and gastrointestinal stromal tumor patients.
"The FDA approval of larotrectinib marks an important milestone in how we treat cancers that have an NTRK gene fusion -- a rare driver of cancer," investigator David Hyman, MD, of Memorial Sloan Kettering Cancer Center in New York City, said in a . "I have seen firsthand how treatment with larotrectinib, which is designed specifically for this oncogenic driver, can deliver clinically meaningful responses in patients with TRK fusion cancer, regardless of patient age or tumor type."
Data from the trials were first presented by Hyman at last year's American Society of Clinical Oncology meeting.
Larotrectinib, indicated for adult and pediatric patients with NTRK-positive tumors and no acquired resistance mutation, is the second "tissue agnostic" approval from the agency, following last year's approval of pembrolizumab (Keytruda) for any microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) unresectable or metastatic solid tumor.
"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 FDA Commissioner Scott Gottlieb, MD, in a announcing the approval.
"Its approval reflects advances in the use of biomarkers to guide drug development and the more targeted delivery of medicine," Gottlieb continued. "This type of drug development program, which enrolled patients with different tumors but a common gene mutation, wouldn't have been possible a decade ago because we knew a lot less about such cancer mutations."
Common adverse events (AEs) in the larotrectinib trials included increased alanine transaminase and aspartate transaminase (45% each), anemia (42%), fatigue (37%), nausea (29%), dizziness (28%), vomiting (26%), cough (26%), constipation (23%), and diarrhea (22%).
The FDA warns that larotrectinib should not be taken by women who are either pregnant or breastfeeding due to possible harms to the fetus or baby, and that patients should be monitored for neurologic reactions (e.g., dizziness). Neurologic events of any grade in studies of patients with and without the NTRK fusion occurred in more than half of participants (53%), with 6% experiencing grade 3 AEs and 0.6% experiencing grade 4 AEs.