The US FDA have recently approved the first-ever tyrosine receptor kinase inhibitor (TRK) drug to be used in the treatment of tumors with neurotrophic receptor tyrosine kinase (NTRK) gene fusion, in cases with no available alternative treatments. It’s only the second time the FDA has approved a cancer drug’s use based on a certain mutation rather than a particular tumor type.
The approval of the drug, known as larotrectinib (brand name Vitrakvi®), is based on the overall response rate (ORR) and duration of response that was shown in clinical trials. The trial demonstrated a 75% ORR with 22% showing complete response and 53% showing partial response. Continued approval will be dependent on the results and observed clinical benefit in confirmatory trials.
NTRK gene fusions are alternations in the genome that give constitutively-activated TRK fusion proteins. Such proteins can be oncogenic and are involved in promoting tumor cell proliferation and survival. These fusions can be found in both adult and pediatric patients across a variety of solid tumor types such as lung, thyroid or melanoma to name a few.
Patients eligible for larotrectinib should be selected based on the presence of the NTRK gene fusion in their tumor cells, which can be done using tests such as next-generation DNA sequencing or fluorescence in situ hybridization.
“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. 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,” commented trial principal investigator David Hyman of Memorial Sloan Kettering Cancer Center (NY, USA); “We now have the first therapy approved for this genomic alteration, regardless of cancer type.”
Robert LaCaze of Bayer’s Pharmaceuticals division (NJ, USA) commented: “Today’s approval of Vitrakvi is the culmination of years of hard work and research by many people to bring the first ever treatment to patients with TRK fusion cancer. TRK fusions are rare, but occur across many different tumor types.”
It should be noted that larotrectinib showed potential side effects of neurotoxicity, hepatotoxicity and embryo-fetal toxicity. More than 20% of patients in the study experienced some form of side effect though most with low grade severity; these included anemia, nausea, dizziness, constipation, diarrhea and vomiting.