The U.S. Food and Drug Administration (FDA) approved Vitrakvi® (larotrectinib), the first ever oral TRK inhibitor, for the treatment of adult and pediatric 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. In 2025, Vitrakvi received full FDA approval. The full approval of Vitrakvi is based on the results of confirmatory trials that support Vitrakvi as a potential new standard of care treatment option for NTRK gene fusion-positive tumors in adult and pediatric patients.
Vitrakvi was the first treatment to receive a tumor-agnostic indication at the time of initial FDA approval and additional precision medicines targeting the fusion are now available. In clinical trials of patients with TRK fusion cancer, Vitrakvi demonstrated a response rate of 75 percent including a 22% complete response rate.2
Clinical data from three Vitrakvi clinical trials in patients whose tumors harbor tropomyosin receptor kinase (TRK) fusions demonstrating a 76% confirmed objective response rate were recently published in the New England Journal of Medicine after an initial summary presentation at the American Society of Clinical Oncology.1,2
Vitrakvi received Breakthrough Therapy Designation from the FDA in July 2016, for the treatment of unresectable, or metastatic solid tumors with NTRK-fusion proteins in adult and pediatric patients who require systemic therapy and who have either progressed following prior treatment or who have no acceptable alternative treatments. Vitrakvi appears to deliver consistent and durable responses in TRK fusion patients across all ages with few side effects.
Rare Mutation
Vitrakvi is a potent, oral and selective precision cancer medicine for the treatment of patients with cancers that harbor abnormalities involving the tropomyosin receptor kinases (TRKs). Growing research suggests that the NTRK genes, which encode for TRKs, can become abnormally fused to other genes, resulting in growth signals that can lead to cancer in many sites of the body. Vitrakvi targets the TRK fusion gene which occurs rarely in sarcomas fibrosarcomas and a variety of other cancers.
Response to Vitrakvi by primary cancer location
TRK fusions are chromosomal abnormalities that occur when one of the NTRK genes (NTRK1, NTRK2, NTRK3) becomes abnormally connected to another, unrelated gene (e.g. ETV6, LMNA, TPM3). This abnormality results in uncontrolled TRK signaling that can lead to cancer. TRK fusions occur rarely but broadly in various adult and pediatric solid tumors including sarcomas, fibrosarcomas, and gastrointestinal stromal tumors (GIST). Although TRK fusions can be identified through various next-generation sequencing tests, patients should ask their physician if the test they order specifically “looked for NTRK fusions” because not all commercially available tests measure NTRK.
The Vitrakvi TRK fusion story fulfills the promise of precision medicine, where tumor genetics rather than tumor site of origin define the treatment approach. It is now incumbent upon the clinical oncology and pathology communities to examine our testing paradigms, so that TRK fusions and other actionable biomarkers become part of the standard sarcoma patient workup.
Vitrakvi in NSCLC
The overall response rate was 73% with a median duration of response in 15 advanced NSCLC patients. Progression-free survival, and overall survival were 34 months, and 41 months respectively. Among patients with CNS metastases, the response rate was 63%.
Augtyro (repotrectinib)
In June 2024 The US Food and Drug Administration granted accelerated approval to Augtyro (repotrectinib) as a treatment for patients with refractory solid tumors harboring NTRK gene fusions. To be eligible for Augtyro, patients must have progressed on prior treatments and be ineligible for surgical resection.
The FDA based its decision on the results of the Phase I-II Trident clinical trial in which 88 patients received Augtyro. Of these patients, 48 had received prior TRK inhibitors and 40 had not. Among those who had not received TRK inhibitors before, the overall response rate was 58% and the median duration of response was not reached at data cutoff. In patients who had received prior TRK inhibitors, the overall response rate was 50% and the median duration of response was 9.9 months.
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References:
- http://www.bayer.us/en/newsroom/press-releases/article/?id=123256
- http://www.nejm.org/doi/full/10.1056/NEJMoa1714448?query=featured_home
- mavendoctors.io/cancerconnect/lung-cancer/early-imaging-with-pet-does-not-reduce-number-of-diagnostic-tests-for-cancer-guVoQHxUQEOdeKOTHRo75g/
- Drilon A, Tan D, Lassen U, et al. JCO Precis Oncol. 2022 Jan;6:e2100418. doi:10.1200/PO.21.00418.
