Repotrectinib can overcome some ROS1 mutations that cause drug resistance. The FDA sanctioned this innovative therapy in 2023 for use as eit...
 |
| Repotrectinib can overcome some ROS1 mutations that cause drug resistance. |
The FDA sanctioned this innovative therapy in 2023 for use as either a primary or subsequent line of treatment for patients with ROS1-positive non-small cell lung cancer (NSCLC), showcasing a significant advancement in the fight against this disease.
In a pivotal move by the Food and Drug Administration (FDA) in November 2023, repotrectinib, known commercially as (Augtyro), received approval for its use in treating specific advanced lung cancers characterized by a ROS1 gene fusion mutation.
The full results from the clinical trial that underpinned repotrectinib's approval have now been disclosed. The studies published in the New England Journal of Medicine on January 11, the study reports that close to 80% of participants with NSCLC who had not previously been treated with a ROS1-targeted drug had significant tumor reduction. Furthermore, around 40% of those previously treated with a ROS1 inhibitor, like crizotinib (Xalkori) or entrectinib (Rozlytrek), also saw their tumors shrink.
The FDA’s endorsement of repotrectinib as both an initial and second-line treatment for advanced or metastatic NSCLC with ROS1 fusions highlights its effectiveness. The TRIDENT-1 trial, which evaluated repotrectinib's efficacy in individuals with advanced solid tumors, including 127 with ROS1 fusion-positive metastatic, demonstrated prolonged responses in many patients.
"Repotrectinib promises enduring outcomes for patients with ROS1 fusion-positive lung cancers, irrespective of their prior targeted therapy history," stated Alexander Drilon, M.D., from the Memorial Sloan Kettering Cancer Center and lead investigator of the TRIDENT-1 study.
 |
| Signs that reveal a person might has a lung cancer. |
The trial also revealed repotrectinib's ability to diminish tumors that had metastasized to the brain, a frequent complication of lung cancer. Its design to counteract ROS1 mutations that confer resistance to other drugs, including the G2032R mutation, was particularly noteworthy, with a response rate of 59% in affected patients.
Luis Raez, M.D., from the Memorial Cancer Institute in Florida and a study collaborator, noted, "Repotrectinib successfully addresses resistant mutations that other ROS1 inhibitors cannot, without increasing side effects." Experts are now calling for further studies to optimize the use of ROS1-targeted therapies based on individual patient needs.
Repotrectinib inhibits the activity of the ROS1 fusion protein, offering a new treatment avenue for up to 2% of NSCLC patients with this genetic anomaly. Unlike previous ROS1 inhibitors, repotrectinib, taken orally, is effective against a broader range of mutations and also targets additional proteins that promote cancer growth.
The TRIDENT-1 trial showcased impressive long-term responses and progression-free survival rates, with significant effects even on brain metastases. Despite its promising results, repotrectinib's side effects like dizziness were manageable through dose adjustments.
The trial's limitations include the lack of a direct comparison to other ROS1 inhibitors and the small participant number, reflective of the rarity of ROS1 fusion NSCLC. Yet, the robust responses and manageable side effects position repotrectinib as a critical option for patients, especially those who have exhausted other treatments.