KEY TAKEAWAYS
- The LIBRETTO-431 phase III aimed to compare selpercatinib to chemotherapy for newly diagnosed RET fusion-positive NSCLC.
- The primary endpoint of PFS, assessed by BICR, was evaluated in both the ITT-pembro and ITT populations.
- The result demonstrated that selpercatinib significantly outperformed chemotherapy plus pembrolizumab in extending PFS in advanced RET-positive NSCLC.
Selpercatinib, an effective RET inhibitor, has not been previously assessed in a randomized trial for RET-positive non-small cell lung cancer (NSCLC). Researchers aimed to compare selpercatinib to chemotherapy for newly diagnosed RET fusion-positive NSCLC.
The primary endpoint, progression-free survival (PFS), was initially assessed by blinded independent central review (BICR) in patients(pts) stratified by the investigator’s intent to treat with pembrolizumab if assigned to the control arm (ITT-pembro). The analysis was extended to the entire intent-to-treat (ITT) population.
The planned interim efficacy analysis by BICR occurred after 98 PFS events in the ITT-pembro population. Crossover to selpercatinib was permitted following BICR progression on the control arm.
About 261 pts were enrolled from 23 countries, and baseline characteristics were balanced across study arms. With a median follow-up of approximately 19 months, selpercatinib demonstrated superior PFS compared to the control in both the ITT-pembro population (HR: 0.465, 95% CI: 0.309, 0.699; p-value: 0.0002) and the overall ITT population (HR: 0.482, 95% CI: 0.331, 0.700; p-value: 0.0001).
In the ITT-pembro population, the median PFS was 24.8 months (95% CI: 16.9, NE) with selpercatinib vs 11.2 months (95% CI: 8.8, 16.8) with the control. Selpercatinib also showed clinically meaningful improvements in objective ORR, duration of response (DOR), and intracranial response compared to the control.
The time to the central nervous system (CNS) progression was longer with selpercatinib than with the control (cause-specific HR 0.26; 95% CI: 0.11, 0.59; P=0.0006). Adverse events observed with selpercatinib and the control arm were generally consistent with those previously reported.
The result demonstrated that selpercatinib significantly outperformed chemotherapy plus pembrolizumab in extending PFS in advanced RET-positive NSCLC.
Clinical Trial: https://clinicaltrials.gov/study/NCT04194944
Loong HHF, Goto K, Solomon BJ, Park K, Pérol M, Arriola E, Novello S, Cheng Y, Ardizzoni A, Mak M, Santini FC, Elamin YY, Drilon A, Wolf J, Han B, Han H, Uh M, Puri T, Ilaria V, Zhou C. Randomized phase III study of first-line selpercatinib versus chemotherapy and pembrolizumab in RET fusion-positive NSCLC. Presented by H.H.F. Loong at ESMO 2023. LBA4.
