Characterization and clinical management of adverse events following treatment with repotrectinib: a TRIDENT-1 analysis

Drilon, A; Cho, BC; Camidge, DR; Nagasaka, M; Besse, B; Solomon, B; Goto, K; Wolf, J; Popat, S; Felip, E; Yang, N; de Langen, AJ; Lu, S; Velcheti, V; Lin, AL; Calvet, CY; Li, L; Tschaika, M; Afsar, S; Yang, H; Lin, JJ

Author(s): Drilon, A; Cho, BC; Camidge, DR; Nagasaka, M; Besse, B; Solomon, B; Goto, K; Wolf, J; Popat, S; Felip, E; Yang, N; de Langen, AJ; Lu, S; Velcheti, V; Lin, AL; Calvet, CY; Li, L; Tschaika, M; Afsar, S; Yang, H; Lin, JJ;
Details: Publication Year 2026-05-08,Volume 31,Issue #6,Page oyag137
Journal Title: Oncologist
Publication Type: Research article
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.
Publisher: Oxford University Press
Keywords: Humans; Male; Female; Middle Aged; *Pyrazoles/adverse effects/administration & dosage/therapeutic use; Adult; Aged; *Lung Neoplasms/drug therapy/pathology; *Carcinoma, Non-Small-Cell Lung/drug therapy/pathology; *Pyrimidines/adverse effects/administration & dosage/therapeutic use; *Protein Kinase Inhibitors/adverse effects/therapeutic use; *Drug-Related Side Effects and Adverse Reactions/pathology; Aged, 80 and over; Nsclc; Repotrectinib; Trident-1; clinical management; safety management
Department(s): Medical Oncology
Publisher's Version: https://doi.org/10.1093/oncolo/oyag137
Open Access at Publisher's Site: https://doi.org/10.1093/oncolo/oyag137
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2026-04-28 02:39:56

Last Modified: 2026-05-14 12:09:39