Patient-Reported Outcomes From LIBRETTO-431: First-Line Selpercatinib Versus Chemotherapy With Pembrolizumab in RET...

Area of Science:

• Oncology
• Clinical Trials
• Patient-Reported Outcomes

Background:

• Advanced RET fusion-positive non-small cell lung cancer (NSCLC) presents a significant treatment challenge.
• First-line treatment options historically include platinum-based chemotherapy, often combined with pembrolizumab.
• Selpercatinib has emerged as a targeted therapy with demonstrated efficacy in this patient population.

Purpose of the Study:

• To evaluate patient-reported outcomes (PROs) from the LIBRETTO-431 trial comparing first-line selpercatinib to chemotherapy in advanced RET fusion-positive NSCLC.
• To assess the impact of selpercatinib on symptom burden, quality of life, and tolerability.

Main Methods:

• The LIBRETTO-431 trial randomized 129 patients to selpercatinib and 83 to platinum chemotherapy with pembrolizumab.
• Key PRO endpoints included time to confirmed deterioration (TTCD) of NSCLC Symptom Assessment Questionnaire (NSCLC-SAQ) scores and European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire.
• Patient-reported tolerability was assessed using the Functional Assessment of Cancer Therapy GP5 item (GP5).

Main Results:

• Selpercatinib significantly delayed TTCD for all NSCLC-SAQ symptoms and demonstrated clinically meaningful improvement in the NSCLC-SAQ total score at 1 year.
• Patients receiving selpercatinib experienced delayed TTCD of physical and role functioning, with significantly improved physical functioning.
• Selpercatinib showed better patient-reported tolerability, with a lower proportion of patients bothered by side effects (22.6% vs. 39.7%).

Conclusions:

• Patient-reported outcomes from the LIBRETTO-431 trial strongly support the benefit of first-line selpercatinib in advanced RET fusion-positive NSCLC.
• These PROs, alongside established efficacy and safety, reinforce selpercatinib as a standard of care.
• The findings underscore the importance of early genomic testing for RET fusions in NSCLC management.