Vitrakvi Second Drug Approved Based on a Genetic Biomarker, Not a Tumor Type

December 2018, Vol 9, No 4 - FDA Approvals, News & Updates


On November 26, 2018, the FDA accelerated the approval of larotrectinib (Vitrakvi; Loxo Oncology/Bayer) for the treatment of patients whose cancers have a specific genetic biomarker. This is the second drug to receive FDA approval based on a biomarker rather than a specific tumor type or site. The first drug to receive this type of approval was pembrolizumab (Keytruda), in 2017.

Larotrectinib is indicated for the treatment of patients with solid tumors associated with a neurotrophic receptor tyrosine kinase (NTRK) gene fusion and no acquired resistance mutation, and for patients with metastatic cancer or those in whom tumor resection is likely to lead to severe morbidity and who have no appropriate alternative treatments or whose disease progressed after appropriate treatment. The FDA granted larotrectinib breakthrough therapy and orphan drug designations.

Some of the tumors with an NTRK fusion that responded to larotrectinib therapy were soft-tissue sarcoma, salivary gland cancer, infantile fibrosarcoma, and thyroid and lung cancers.

This new approval marks a paradigm shift in the development of oncology drugs that are “tissue agnostic,” following a guidance issued by the FDA in early 2018.

“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. “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,” he added. “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.”

The NTRK genes, which encode for TRK proteins, can become abnormally fused to other genes, resulting in growth signals that support tumor growth. NTRK fusions are rare, but they occur in cancers arising in many body sites. This is the first treatment to receive FDA approval for cancer that includes NTRK mutation.

The efficacy of larotrectinib was determined based on 3 clinical trials that included 55 patients (children and adults) with metastatic solid tumors that had an identified NTRK gene fusion and no resistance mutation or in whom surgical resection was likely to lead to severe morbidity. These patients had no appropriate treatment available or their cancer progressed after treatment.

The overall response rate with larotrectinib was 75% across different types of solid tumors. Overall, 73% of responses lasted ≥6 months, and 39% lasted ≥1 year at the time of data analysis.

The common side effects reported with larotrectinib include fatigue, nausea, cough, constipation, diarrhea, dizziness, vomiting, and increased aspartate aminotransferase and alanine aminotransferase levels.