FDA OKs Bayer/Loxo Targeted Cancer Drug
FDA has approved Bayer and Loxo Oncology’s Vitrakvi (larotrectinib) for treating adult and pediatric cancers in patients who have a specific genetic feature (biomarker). The accelerated approval drug is indicated for treating patients with solid tumors that have a neurotrophic receptor tyrosine kinase (NTRK) gene fusion without a known acquired resistance mutation, are metastatic or where surgical resection is likely to result in severe morbidity and have no satisfactory alternative treatments or that have progressed following treatment, according to an FDA release.
“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,” FDA commissioner Scott Gottlieb is quoted in the release as saying. “This new site-agnostic oncology therapy isn’t specific to a cancer arising in a particular body organ, such as breast or colon cancer. Its approval reflects advances in the use of biomarkers to guide drug development and the more targeted delivery of medicine. We now have the ability to make sure that the right patients get the right treatment at the right time. 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.”
FDA also said that the therapy’s approval followed policies that the agency developed in a guidance document entitled “Developing Targeted Therapies in Low-Frequency Molecular Subsets of a Disease.” Approval was based on clinical data showing a supportive overall response rate (ORR) and duration of response (DOR). The companies say that in pooled study results, Vitrakvi demonstrated an ORR of 75% (with 22% of patients achieving a complete response and 53% of patients achieving a partial response) across various tumor types, including soft tissue sarcoma, salivary gland, infantile fibrosarcoma, thyroid, lung, melanoma, colon, GIST, cholangiocarcinoma, appendix, breast and pancreas. Additionally, 73% of responding patients had a DOR lasting six months or greater at the time of data cut-off.
Vitrakvi has warnings and precautions of neurotoxicity, hepatotoxicity and embryo-fetal toxicity, the companies say. The most common adverse events included anemia, fatigue, nausea, dizziness, cough, vomiting, constipation, and diarrhea.
The companies note that TRK fusion cancer occurs across different tumor types with varying frequency in both adult and pediatric patients. It is diagnosed by identifying NTRK gene fusions using specific tests, including those that employ next-generation sequencing and fluorescence in situ hybridization. “Patients eligible for treatment with Vitrakvi should be selected based on the presence of an NTRK gene fusion in their tumor,” they add.