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Gregory J. Riely, MD, PhD
Gregory J. Riely, MD, PhD
Posted: Wednesday, September 25, 2024
Results of the phase II TRUST-I study—reportedly the largest prospective clinical trial to date conducted in patients living with ROS1-rearranged non–small cell lung cancer (NSCLC)—indicate that the next-generation tyrosine kinase inhibitor (TKI) taletrectinib may be an effective, safe option for those who are TKI-naive. The findings also suggest that taletrectinib may “overcome common mechanisms of resistance to crizotinib and provide benefit in the crizotinib-pretreated setting,” wrote Caicun Zhou, MD, PhD, of the Tongji University School of Medicine, Shanghai, and colleagues in the Journal of Clinical Oncology.
A total of 173 patients, all from China, were enrolled in the trial as of November 2023: 106 TKI-naive and 67 pretreated with crizotinib. Nearly 75% had never smoked.
In TKI-naive patients, the confirmed objective response rate and the intracranial confirmed objective response rate were 91% and 88%, respectively. In crizotinib-pretreated patients, the corresponding figures were 52% and 73%.
The median duration of response and median progression-free survival—two secondary endpoints—were not reached in TKI-naive patients, with 22.1-month and 23.5-month follow-up, respectively. In crizotinib-pretreated patients, the median duration of response was 10.6 months (with an 8.4-month follow-up), and the median progression-free survival was 7.6 months (with a 9.7-month follow-up).
In terms of safety, the most frequent treatment-emergent adverse events were most often of grade 1 or 2. Further, the incidence of neurologic treatment-emergent adverse events was low, and they were mostly grade 1.
Activity against G2032R, an acquired resistance mutation, was also thought to be clinically significant, according to the investigators. A total of 8 of 12 patients (67%) with G2032R mutations responded to treatment.
Disclosure: For full disclosures of the study authors, visit ascopubs.org.
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