Background

LIBRETTO-001 is an ongoing, global, open-label, phase 1/2 study of selpercatinib in patients with advanced or metastatic solid tumors. We report interim patient-reported outcomes in patients with RET fusion-positive non-small-cell lung cancer (NSCLC).

Patients and Methods

Patients completed the EORTC QLQ-C30 version 3.0 at baseline (Cycle 1, Day 1), approximately every other 28-day cycle until Cycle 13, and every 12 weeks thereafter. Data were evaluated through Cycle 13 as few patients had reached later timepoints. A change of ≥10 points from baseline in domain scores was considered clinically meaningful.

Results

Among 253 selpercatinib-treated patients, 239 were categorized into subgroups by prior therapy: treatment-naïve (n=39), 1 prior line of therapy (n=64), or ≥2 prior lines of therapy (n=136). The QLQ-C30 was completed by >85% of patients at each timepoint. Most patients overall and in each subgroup maintained or improved in all health-related quality of life (HRQoL) domains during treatment. The percentage of patients who experienced clinically meaningful improvements ranged from 61.1%–66.7% for global health status, 33.3%–61.1% for dyspnea, and 46.2%–63.0% for pain. The 61.1% of patients with improved dyspnea had ≥2 prior lines of therapy; median time-to-first improvement was 3.4 months. At the first post-baseline evaluation (Cycle 3), 45.9% of all patients reported a ≥10-point reduction in pain.

Conclusion

In this interim analysis, the majority of patients with RET fusion-positive NSCLC remained stable or improved on all QLQ-C30 subscales at each study visit, demonstrating the favorable HRQoL as measured by the QLQ-C30 during treatment with selpercatinib.

Implications for Practice

Patients with non-small cell lung cancer (NSCLC) generally experience greater symptom burden and lower health-related quality of life (HRQoL) as disease progresses. In a phase 1/2 trial, improvements in HRQoL were observed in over 60% of patients with advanced RET fusion-positive NSCLC who received selpercatinib, a highly selective RET inhibitor. More than one-third of patients reported a reduction in dyspnea during study participation and nearly half reported a reduction in pain by the first-follow up assessment.