Health-related Quality of Life (HRQoL) and Symptoms in LIBRETTO-431 Patients with RET Fusion-positive Advanced Non-Small-Cell Lung Cancer (NSCLC)

Selpercatinib is approved for the treatment of advanced RET fusion+NSCLC. We report NSCLC symptoms and HRQoL from LIBRETTO-431, a randomized phase 3 trial, comparing first-line selpercatinib to platinum-based chemotherapy (CT)+/- pembrolizumab.

Data were used from the intent-to-treat (ITT) pembrolizumab subpopulation [selpercatinib (n=129); CT+pembrolizumab (control, n=83)] to assess time to confirmed deterioration (TTCD) of NSCLC symptoms (cough, dyspnea, pain, fatigue, poor appetite using NSCLC-Symptom Assessment Questionnaire [SAQ]). TTCD of NSCLC symptoms were defined as time from randomization to the first score that met the pre-specified meaningful within-patient change thresholds, confirmed at next assessment. TTCD was compared between treatment arms using log-rank test and Cox proportional hazards model. Changes of NSCLC-SAQ total score (meaningful important difference [MID]≥2 points) and HRQoL (using EORTC QLQ-C30 Physical Function (MID≥6 points) and Global Health Status (GHS)/QoL [MID≥5 points]) up to 1 year were evaluated and compared between the arms using a growth curve model and mixed model for repeated measures.

Selpercatinib significantly (p<.05) delayed TTCD of all individual symptoms with hazard ratio ranging from 0.41 (cough and pain) to 0.57 (dyspnea) vs control. Selpercatinib also showed a significant and clinically meaningful difference in the mean NSCLC-SAQ total score (difference=-2.0, p<.001) and physical function (difference=8.1, p=.003) at 1 year vs control. GHS/QoL was improved in both arms with no difference in the mean scores between the arms at 1 year.

Selpercatinib significantly delayed TTCD of NSCLC symptoms and improved physical function compared to control in this patient population after 1 year of treatment. The findings were consistent with the favorable efficacy of selpercatinib compared with platinum-based CT+pembrolizumab and further support first-line use of selpercatinib in this population.

Previously presented at ASCO 2024

Publication History

Article published online:
18 March 2025