Citations 1
Characterization and clinical management of adverse events following treatment with repotrectinib: a TRIDENT-1 analysis
Drilon, Alexander E., Cho, B , Camidge, D Ross, Nagasaka, Misako, Besse, Benjamin, Solomon, B, Goto, Koichi , Wolf, Jürgen, Popat, Sanjay , Felip, Enriqueta, Yang, Nong, Langen, A. de, Lu, Shun, Velcheti, Vamsidhar, Lin, Andrew , Calvet, C. , Tschaika, Marina, Afsar, Salman, Yang, Haisu, Lin, Jessica J., Solomon, Benjamin , Cho, Byoung Chul , Besse, Benjamin , Drilon, Alexander , Langen, Adrianus J. de , Drilon, Alexander , Nagasaka, Misako , Besse, Benjamin , de Langen, Adrianus Johannes , Lin, Andrew L , Popat, Sanjay , Solomon, Benjamin J , Camidge, David Ross , Wolf, Jürgen , Felip, Enriqueta , Yang, Nong, Velcheti, Vamsidhar , Afsar, Salman
The Oncologist | April 14, 2026 | Volume: 31 | Issue: 6 | Pages: No page available
Abstract Background Repotrectinib, a next-generation ROS1/TRK tyrosine kinase inhibitor, is approved for ROS1 fusion-positive non-small cell lung cancer and NTRK fusion-positive solid tumors. Its side effects and safety management strategies require further characterization. Patients and Methods The safety profile of repotrectinib (treatment-emergent/related adverse events [TEAEs/TRAEs]) was established in patients who initiated treatment at the recommended dose (160 mg daily [QD] for 14 days, then 160 mg twice daily [BID]) across all cohorts of the global, multicenter phase 1/2 TRIDENT-1 study. AE management strategies were outlined. Results In 472 patients, the most common TRAEs (dizziness [58%] and dysgeusia [50%]) were likely TRK inhibition-related. Median relative dose intensity was 90%; 14% (n = 66/472) of patients did not increase their initial QD dose to BID (mostly due to CNS AEs). Rates of dizziness (median onset, 7 days) were similar in patients with/without baseline brain metastases. Dose modifications downgraded severity or resolved dizziness in 78% of patients; 58% of patients had pharmacologic intervention without dose modification. Dizziness was downgraded/resolved in 62% (n = 120/195) of patients who did not receive dose modification or pharmacologic intervention. Treatment-related cognitive impairment and weight gain occurred in 19% and 12% of patients, respectively. Treatment-emergent withdrawal pain occurred in 14% of patients (median resolution time, 2.1 weeks). Dose interruption and reduction from TRAEs occurred in 39% and 38% of patients, respectively; 10% reported later re-escalation back to 160 mg BID. Conclusion Many repotrectinib AEs, including neurological AEs secondary to TRK inhibition, were mitigated with appropriate management, including dose modification and/or pharmacologic intervention.