Sherif B, Burke M, Besse B, Solomon B, Bazhenova L, Kim DW, Lin JJ, Wolf J, Popat S, Goto K, de Langen AJ, Springfeld C, Reynolds M, Odom D, Yuan Y, Lee A, Blum SI, Thamake S, Ades F, Drilon A. Health-related quality-of-life of patients treated with repotrectinib for neurotrophic tyrosine receptor kinase (NTRK)-positive advanced solid tumors: results From TRIDENT-1. Poster presented at the ISPOR Europe 2023; November 14, 2023. Copenhagen, Denmark. [abstract] Value Health. 2023 Dec; 26(12 Supplement):S484. doi: 10.1016/j.jval.2023.09.2619

OBJECTIVES: In a multi-cohort phase 1/2 study (TRIDENT-1), repotrectinib, a next-generation tyrosine kinase inhibitor (TKI), has shown clinical activity and manageable safety in ROS1+ advanced non-small cell lung cancer (NSCLC) and NTRK+ locally advanced/metastatic solid tumors. We analyzed treatment-related symptoms and general health status in patients with NTRK+ solid tumors using the EORTC QLQ-C30

METHODS: Patients with NTRK+ advanced solid tumors who received either no prior TKI (TKI-naive) or ≤2 prior lines of TKI (TKI-pretreated) received repotrectinib 160 mg once daily for 14 days, followed by twice daily if tolerated. The QLQ-C30 was administered at screening, prior to each cycle, and end-of-treatment visit. Change from baseline in GHS/QOL and each of the functional and symptom scales/items were summarized. Time to first improvement (TFI) and time to definitive deterioration (TDD) were assessed using Kaplan-Meier methods. ≥10-point changes from baseline were prespecified as thresholds for meaningful change. Analysis was conducted on NTRK cohorts using data collected through December 2022.

RESULTS: Among the 79 patients with NTRK+ solid tumors (35 TKI-naïve [median follow-up: 17.8 months [range, 8.7–64.6]) and 44 TKI-pretreated (median follow-up: 20.1 months [8.7–69.4]) analyzed, the most frequent tumor type was NSCLC (43%). Mean baseline GHS/QOL scores were 70.2 in TKI-naïve and 64.9 in TKI-pretreated patients. Mean changes in GHS/QOL and functional scales were stable through the first year on treatment in both groups. Overall, symptom scales were stable, except worsening in Constipation for TKI-naïve. Median TDD in GHS/QOL was 17.5 (95% CI, 9.2–19.3) months for TKI-naïve and 13.1 (8.4–NE) months for TKI-pretreated. Median TFI in GHS/QOL was not reached for either group.

CONCLUSIONS: Patients with NTRK+ solid tumors who were treated with repotrectinib generally experienced stable HRQoL as measured by the QLQ-C30. These results compliment the efficacy and safety profile of repotrectinib as a treatment option for patients with NTRK+ solid tumors.