Patient-Reported Outcomes with Selpercatinib Among Patients with RET Fusion–Positive Non-Small Cell Lung Cancer in the Phase I/II LIBRETTO-001 Trial

Abstract

Background LIBRETTO-001 is an ongoing, global, open-label, phase I/II 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 European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (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 time points. 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), one prior line of therapy (n = 64), or two or more prior lines of therapy (n = 136). The QLQ-C30 was completed by >85% of patients at each time point. 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% to 66.7% for global health status, 33.3% to 61.1% for dyspnea, and 46.2% to 63.0% for pain. The 61.1% of patients with improved dyspnea had two or more prior lines of therapy; median time to first improvement was 3.4 months. At the first postbaseline 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 favorable HRQoL as measured by the QLQ-C30 during treatment with selpercatinib.

Patient-reported outcomes following selpercatinib treatment in Chinese patients with advanced RET fusion-positive non-small-cell lung cancer and thyroid cancer, and RET-mutant medullary thyroid cancer in the phase II LIBRETTO-321 trial

“…The lower risk of experiencing key treatment-associated symptoms has demonstrated the relative tolerability of selpercatinib.Furthermore, previously reported safety data for selpercatinib have demonstrated mild and manageable adverse effects indicating selpercatinib to be a promising treatment option for Chinese patients with RET fusion-positive NSCLC, RET fusion-positive TC, and RET-mutant MTC. The PROs of selpercatinib in the global LIBRETTO-001 trial have also demonstrated favorable outcomes in terms of HRQoL as measured by the QLQ-C30 in most of the patients with RET fusion-positive NSCLC and RETmutant MTC 27,32. Our results in Chinese patients are consistent with the global study.…”

RET signaling pathway and RET inhibitors in human cancer

“…The same clinical trial also determined an objective response of 69-79% in MTC patients bearing RET alterations ( 268 ). Many of these patients (NSCLC or MTC) reported improved or maintained quality of life during treatment with selpercatinib ( 269 , 270 ). Taken together, these results indicate that selpercatinib elicits durable efficacy, including intracranial activity, with primarily low-grade toxicity effects in patients with RET-altered cancers.…”

Exploring histopathological and serum biomarkers in lung adenocarcinoma: Clinical applications and translational opportunities (Review)

“…RET rearrangement is mainly found in young patients without a history of smoking and, like EFGFR or ALK mutations, it is associated with a high probability of metastatic progression in the brain ( 49 ). RET rearrangement is amenable to treatment with selpercatinib and pralsetinib therapy as demonstrated in the LIBRETTO-001 and ARROW clinical trials with response rates of 64% maintained for ~18 months ( 50 , 51 ).…”