Poster Presentation Clinical Oncology Society of Australia Annual Scientific Meeting 2024

Health-related Quality of Life (HRQoL) and Symptoms in LIBRETTO-431 Patients with RET Fusion-positive Advanced Non-Small-Cell Lung Cancer (NSCLC) (#260)

Caicun Zhou 1 , Silvia Novello 2 , Pilar Garrido 3 , Christophe Dooms 4 , Jorge Alatorre-Alexander 5 , Niels Reinmuth 6 , Adrienne M. Gilligan 7 , Nalin Payakachat 7 , Kim Cocks 8 , Gill Worthy 8 , Koichi Goto 9 , Aarohan Pruthi 7
  1. Shanghai Pulmonary Hospital, Shanghai, China
  2. Department of Oncology, AOU San Luigi, Orbassano, University of Torino, Torino, Italy
  3. Medical Oncology Department, Hospital Ramón y Cajal, Universidad de Alcalá, Madrid, Spain
  4. Department of Respiratory Diseases, University Hospitals KU Leuven, Leuven, Belgium
  5. Health Pharma Professional Research, Mexico City, Mexico, USA
  6. Asklepios Lung Clinic, member of the German Center for Lung Research (DZL), Munich-Gauting, Germany
  7. Eli Lilly, Indianapolis, IN, USA
  8. Adelphi Values, Bollington, Cheshire, UK
  9. Department of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa, Japan

LIBRETTO-431 (NCT04194944), a randomized phase 3 trial, compared first-line selpercatinib to platinum-based chemotherapy +/- pembrolizumab. Selpercatinib is approved for the treatment of advanced RET fusion+ NSCLC. This analysis reported NSCLC symptoms and HRQoL from LIBRETTO-431.

Data were used (cut-off date: May 01, 2023) from the intent-to-treat (ITT) pembrolizumab subpopulation [selpercatinib (n=129); chemotherapy + 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), compared to 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, compared to 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 chemotherapy+pembrolizumab and further support 1L use of selpercatinib in this population.

Previously presented at ASCO 2024