Zidesamtinib Offers New Option for ROS1+ NSCLC: Estelamari Rodriguez, MD, MPH

Last month, the FDA approved zidesamtinib (Jideytro; GSK), a novel, brain-penetrant, ROS1-selective inhibitor, for adults with locally advanced or metastatic ROS1-positive non–small cell lung cancer (NSCLC) who have previously received at least 1 ROS1 tyrosine kinase inhibitor (TKI). The decision was based on promising data from the ARROS-1 trial (NCT05118789), a phase 1/2 first-in-human trial for patients with advanced ROS1-positive NSCLC and other solid tumors.

In a recent interview with The American Journal of Managed Care^®, Estelamari Rodriguez, MD, MPH, associate director of community outreach for thoracic oncology and assistant director of diversity, equity, and inclusion at the University of Miami Sylvester Comprehensive Cancer Center, discussed the significance of this approval. She emphasized that zidesamtinib is an important new treatment option for patients with ROS1 fusion–positive NSCLC, which is a relatively small but clinically important subgroup, typically younger, never-smoking patients with a strong predisposition toward brain metastases.

The drug was specifically designed to address 2 major unmet needs: strong intracranial activity and the ability to overcome resistance mechanisms that develop after earlier-generation ROS1 inhibitors such as crizotinib (Xalkori; Pfizer). It was also engineered with an improved safety profile, reducing TrK pathway activation, a mechanism linked to some of the neurologic and other adverse effects seen with older ROS1-targeted therapies.

Because zidesamtinib is approved specifically for use after prior ROS1 TKI therapy, Rodriguez noted it will likely serve as a top second-line option. Among roughly 117 patients in the ARROS-1 trial, many of whom had already received 2 to 3 prior lines of therapy, patients previously treated achieved a 44% response rate, and those with a prior TKI specifically achieved a 49% response rate. Response rates declined among patients who had received more than 2 or 3 prior TKIs, though responses remained durable. About 82% of responders maintained their response for at least 6 months, with many extending to 12 months or longer.

Rodriguez highlighted that these results represent a meaningful, durable option for previously treated ROS1-positive patients, particularly given the drug's strong central nervous system activity, a critical benefit for those prone to brain progression and one with direct implications for quality of life.

“Our patients, especially younger patients who have already progressed, now have a second chance to have a better response, especially responses in the brain, which means a lot for the quality of life of the patients,“ she concluded.