Entrectinib (Rozlytrek™, Genentech, Inc.) has just been FDA approved for use as treatment for patients with cancers containing neurotrophic tyrosine receptor kinase (NTRK) gene fusion, which is a genetic defect. This drug is to be used if there are no other effective treatments available.
This approval marks the third time the FDA has approved a cancer drug based on a biomarker instead of tumor type. These types of approvals are beginning a paradigm in the development of cancer treatments for "tissue agnostic" diseases. Prior drugs approved based on biomarkers include pembrolizumab for tumors with microsatellite instability-high or mismatch repair deficient tumors and larotrectinib for NTRK gene fusion tumors.
Approval was based on four clinical trials that enrolled 54 adults with NTRK fusion-positive tumors. The overall response rate was 57%, and 7.4% of those patients had their tumors disappear completely. Of those 57% responding, 61% of patients had tumor shrinkage persisting nine months or longer. In this population, the most common tumor locations included the lung, salivary gland, breast, thyroid, and the colon/rectum.
In addition, entrectinib was approved for adult patients with metastatic non-small cell lung cancer whose tumors are ROS1-positive. Approval was based on clinical trials that assessed 51 adults with ROS1-positive lung cancer. Entrectinib was effective—the overall response rate was 78%, and 5.9% of patients had their tumors disappear. Of those 78% of patients responding, 55% had tumor shrinkage that lasted 12 months or longer.
The most common treatment-related adverse events of entrectinib include fatigue, constipation, dysgeusia, edema, dizziness, diarrhea, nausea, dysesthesia, dyspnea, myalgia, cognitive impairment, weight gain, cough, vomiting, fever, arthralgia, and vision disorders. The more serious side effects of entrectinib include congestive heart failure, central nervous system effects, skeletal fractures, hepatoxicity, hyperuricemia, and vision disorders.
"We are in an exciting era of innovation in cancer treatment as we continue to see development in tissue agnostic therapies, which have the potential to transform cancer treatment. We're seeing continued advances in the use of biomarkers to guide drug development and the more targeted delivery of medicine," commented Ned Sharpless, MD, FDA Acting Commissioner. "Using the FDA's expedited review pathways, including breakthrough therapy designation and accelerated approval process, we're supporting this innovation in precision oncology drug development and the evolution of more targeted and effective treatments for cancer patients. We remain committed to encouraging the advancement of more targeted innovations in oncology treatment and across disease types based on our growing understanding of the underlying biology of diseases."
For More Information
Paz-Ares L, Doebele RC, Farago AF, et al (2019). Entrectinib in NTRK fusion-positive non-small cell lung cancer (NSCLC): integrated analysis of patients (pts) enrolled in STARTRK-2, STARTRK-1 and ALK-372-001. Ann Oncol, 30(suppl_2). DOI:10.1093/annonc/mdz063.011
Image Credit: Nephron. Courtesy of Wikimedia Commons. Licensed under CC BY-SA 3.0.