First-line Selpercatinib or Chemotherapy and Pembrolizumab in Patients From East Asia With RET Fusion-Positive NSCLC: A LIBRETTO-431 Subgroup Analysis

Abstract

Introduction: Selpercatinib's consistent efficacy and manageable safety profile were observed in patients with RET fusion-positive NSCLC across geographies in single-arm studies (LIBRETTO-001 and LIBRETTO-321). Here, we report the efficacy and safety of the phase 3 study LIBRETTO-431 in patients from East Asia.

Methods: LIBRETTO-431 (NCT04194944) is a randomized, open-label phase 3 trial comparing first-line selpercatinib versus pemetrexed and platinum with or without pembrolizumab. Geography (East Asia versus non-East Asia) was a stratification factor. Efficacy end points including progression-free survival (PFS), objective response rate, and duration of response as assessed by means of blinded independent central review were evaluated in patients from East Asia. Pharmacokinetics were assessed in the selpercatinib group. Safety data were collected for all patients who received at least one dose of study treatment.

Results: Of the 261 patients enrolled, 142 (54.4%) were from East Asia, with 116 randomized to the intention-to-treat-pembrolizumab population (selpercatinib: n = 75, control: n = 41). With a median follow-up of 19.4 and 21.2 months in the selpercatinib and control groups respectively, the median PFS in patients from East Asia was not yet reached for selpercatinib (95% confidence interval (CI): 16.4-not evaluable) versus 11.1 months (95% CI: 7.0-16.8) for control (hazard ratio: 0.38 [95%CI: 0.22-0.68]; p = 0.0008). Safety and pharmacokinetics were consistent with those previously reported across the development program and adverse events were generally manageable with dose adjustments.

Conclusions: Consistent with results in the overall LIBRETTO-431 population, selpercatinib exhibited superior PFS compared with chemotherapy plus pembrolizumab in patients from East Asia with a manageable safety profile. These data further highlight the importance of early comprehensive genomic testing and the use of selpercatinib as a preferred first-line regimen in patients with RET fusion-positive NSCLC across geographies.

Keywords: East Asia; Non–small cell lung cancer (NSCLC); RET fusion; Selpercatinib.

Figure 1

Progression-free survival assessed by blinded independent central review in the intention-to-treat pembrolizumab population. Kaplan-Meier estimate of progression-free survival assessed by blinded independent central review in the patients from East Asia in the intention-to-treat pembrolizumab population. CI, confidence interval; HR, hazard ratio.

Figure 2

Adverse events among patients from East Asia in the safety population. The tornado plot includes AEs that occurred during treatment in at least 15% of the patients in either group. The terms used to describe the AEs are adapted from or composites of the Medical Dictionary for Regulatory Activities, Version 25.0, preferred terms. AE, adverse event; ALT, alanine aminotransferase; AST, aspartate aminotransferase; ECG, electrocardiogram; n, no. of patients in the subgroup.