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

Area of Science:

• Oncology
• Pharmacology
• Clinical Trials

Background:

• Repotrectinib is a next-generation tyrosine kinase inhibitor targeting ROS1 and TRK.
• It is approved for ROS1 fusion-positive non-small cell lung cancer and NTRK fusion-positive solid tumors.
• Characterizing its safety profile and management strategies is crucial.

Purpose of the Study:

• To evaluate the safety profile of repotrectinib.
• To outline strategies for managing treatment-emergent adverse events (TEAEs) associated with repotrectinib.
• To assess the impact of management strategies on adverse event resolution and dose intensity.

Main Methods:

• Safety data were collected from 472 patients in the global, multicenter TRIDENT-1 phase 1/2 study.
• Patients initiated repotrectinib at a recommended dose (160 mg QD, then 160 mg BID).
• Adverse event management strategies, including dose modification and pharmacologic intervention, were analyzed.

Main Results:

• The most common treatment-related adverse events (TRAEs) were dizziness (58%) and dysgeusia (50%), likely due to TRK inhibition.
• 14% of patients did not escalate to the BID dose, primarily due to central nervous system (CNS) adverse events.
• Dose modifications or pharmacologic interventions successfully mitigated dizziness in a significant proportion of patients (78% and 58%, respectively).
• Other TRAEs included cognitive impairment (19%), weight gain (12%), and withdrawal pain (14%).
• Dose interruption or reduction due to TRAEs occurred in 39% and 38% of patients, respectively.

Conclusions:

• Many repotrectinib-related adverse events, particularly neurological events from TRK inhibition, can be effectively managed.
• Dose modification and pharmacologic interventions are key strategies for mitigating these side effects.
• These management approaches help maintain treatment continuity and improve patient outcomes.