by Dr. C.H. Weaver M.D. updated 8/2019
The US Food and Drug Administration (FDA) granted accelerated approval to Rozlytrek (entrectinib) for treatment of adults and pediatric patients 12 years of age and older with solid tumors that have a neurotrophic tyrosine receptor kinase (NTRK) gene fusion.
The FDA previously approved the precision cancer medicine Vitrakvi (larotrectinib) for the treatment of adult and pediatric solid tumors that have a NTRK gene fusion.
These approvals represents a major paradigm shift in how doctors and their patients will need to think about cancer treatment. Until recently we thought of breast cancer cells as having a unique biomarker target that could be treated with a precision cancer medicine. Now, in effect, the biomarker defines the cancer rather than the organ where the cancer began.
The approval of Rozlytrex for patients with the NTRK gene fusion marks the third FDA approval of a “tissue agnostic” cancer therapy based on a biomarker frequently found across different tumor types versus the location in the body where the tumor originated.
Vitrakvi was the second “tissue agnostic” drug approved for the treatment of cancer this year. The first “tissue agnostic” FDA approval was for Keytruda (pembrolizumab) for adult and pediatric patients with unresectable or metastatic, microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) solid tumors that have progressed following prior treatment.
According to the FDA Commissioner Dr. Scott Gottlieb, M.D. "These approvals mark another step in an important shift toward treating cancers based on their tumor genetics rather than their site of origin in the body.”
The shift away from organ specific treatments creates some unique challenges for cancer patients and their doctors and provides hope to many individuals with hard to treat cancers who can now look to genomic testing as another way to identify their available treatment options.
Rozlytrek was evaluated in 54 adult patients with NTRK-positive cancers at various doses and schedules in one of three clinical trials: ALKA, STARTRK-1 (NCT02097810) and STARTRK-2 (NCT02568267). Identification of positive NTRK gene fusion status was determined in local laboratories or a central laboratory using nucleic acid-based tests prior to enrollment.
Among the 54 adult patients, the overall response rate was 57% and the response duration was 6 months or longer for 68% of patients and 12 months or longer for 45% of patients. The most common cancers treated in the trial were sarcoma, non-small cell lung cancer (NSCLC), thyroid, and colorectal cancer.
The most common side effects occurring in at least 20% of patients were fatigue, constipation, dysgeusia, edema, dizziness, diarrhea, nausea, dysesthesia, dyspnea, myalgia, cognitive impairment, increased weight, cough, vomiting, pyrexia, arthralgia, and vision disorders.
Additional Recommended Reading:
- About Vitrakvi® (larotrectinib) for soft tissue sarcoma, salivary gland cancer, infantile fibrosarcoma, thyroid cancer, and lung cancer.
- About Keytruda (pembrolizumab) for adult and pediatric patients with unresectable or metastatic, microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) solid tumors
- Understanding Precision Cancer Medicine: What Every Patient Should Know
- Join The Conversation and Share Your Thoughts
- US Food and Drug Administration. FDA approves third oncology drug that targets a key genetic driver of cancer, rather than a specific type of tumor. August 15, 2019. <a href="https://www.fda.gov/news-events/press-announcements/fda-approves-third-oncology-drug-targets-key-genetic-driver-cancer-rather-specific-type-tumor.">https://www.fda.gov/news-events/press-announcements/fda-approves-third-oncology-drug-targets-key-genetic-driver-cancer-rather-specific-type-tumor.</a> Accessed August 15, 2019.