Dr Raez on the FDA Approval of Repotrectinib in NTRK+ Solid Tumors

Luis E. Raez, MD, FACP, FCCP, hematology/oncology, medical director, chief scientific officer, Memorial Cancer Institute, Memorial Healthcare System, clinical professor of medicine, Florida International University, research professor, Florida Atlantic University, visiting professor of medicine, Cayetano Heredia University, Peru, discusses the significance of the FDA approval of repotrectinib (Augtyro) in solid tumors harboring an NTRK gene fusion.

In June, 2024, the FDA granted accelerated approval to repotrectinib for the treatment of adult and pediatric patients aged 12 years and older with NTRK-mutant solid tumors; these patients will have locally advanced or metastatic disease. This treatment was also approved for patients where surgical resection is likely to result in severe morbidity, or that have progressed after treatment or have no satisfactory alternative therapy.

The approval was based on data from the phase 1/2 TRIDENT-1 study (NCT03093116), which demonstrated that repotrectinib achieved a confirmed overall response rate (cORR) of 58% (95% CI, 41%-73%) in treatment-naive patients (n = 40) as evaluated by blinded independent central review (BICR) and RECIST 1.1 criteria. The median duration of response (DOR) for this group was not estimable (95% CI, NE-NE), indicating a potentially long-lasting benefit. In patients who had previously received a TKI (n = 48), repotrectinib generated a cORR of 50% (95% CI, 35%-65%), with a median DOR of 9.9 months (95% CI, 7.4-13.0).

Genetic aberrations, such as NTRK fusions, are significant in oncology because they are not confined to a single type of tumor but can be found across various cancers in both adult and pediatric patients, Raez begins. The approval of repotrectinib reflects a shift toward agnostic approvals, meaning that the drug is effective across multiple cancer types as long as the tumor harbors the targeted genetic mutation, he explains. This approach marks a departure from traditional cancer treatments that are typically approved for specific types of cancer, like lung or breast cancer, Raez notes.

Patients with these genetic aberrations often have limited treatment options and typically receive palliative chemotherapy, which often result in short-term survival benefit with considerable adverse effects, Raez continues. Repotrectinib represents a significant advancement, offering the potential to extend survival by 2 to 4 years, he says. Accordingly, patients who receive this agent may experience better quality of life compared to those who receive conventional palliative care, Raez explains. The development and approval of drugs targeting genetic aberrations like NTRK are crucial in providing new, effective treatment options that can significantly improve patient outcomes in a variety of cancers, Raez concludes.