Patients with RET Fusion Positive Early Stage Non-Small Cell Lung Cancer Benefit from Selpercatinib: LIBRETTO-432 Early Results An interview with: Jonathan W. Goldman MD, Director of Clinical Trials i
Patients with RET Fusion Positive Early Stage Non-Small Cell Lung Cancer Benefit from Selpercatinib: LIBRETTO-432 Early Results
An interview with:
Jonathan W. Goldman MD, Director of Clinical Trials in Thoracic Oncology, University of California Los Angeles, USA.
Comment from:
David R Spigel MD, President & Chief Medical Officer, Sarah Cannon Research Institute, Nashville, Tennessee, USA
David R. Spigel MD
CHICAGO, USA—The drug selpercatinib, already licensed for treating patients whose advanced non-small cell lung cancers test positive for the RET fusion alteration, has now shown early promise in a study using it as adjuvant therapy in patients with stage One-B to Three-A RET fusion positive tumors.
Findings from the LIBRETTO-432 trial were reported at the 2026 Annual Meeting of the American Society of Clinical Oncology by Jonathan W. Goldman MD, Director of Clinical Trials in Thoracic Oncology at the University of California Los Angeles, California, USA, who discussed the findings with Peter Goodwin. Peter then heard comments from David R Spigel MD, President and Chief Medical Officer at the Sarah Cannon Research Institute, Nashville, Tennessee, USA
AUDIO JOURNAL OF ONCOLOGY: Jonathan Goldman MD and David Spigel MD
IN: [GOODWIN]”I am at the ……
OUT: …..Audio Journal of Oncology, I’m Peter Goodwin 9:39 secs
ASCO 2026 Abstract LBA3:
Event-free survival with adjuvant selpercatinib in stage IB-IIIA RET fusion-positive NSCLC: Primary results of the phase 3 LIBRETTO-432 trial.
First Author: Jonathan Goldman
University of California Los Angeles, Los Angeles, CA
Background:
Selpercatinib, a highly selective, potent and brain-penetrant RET inhibitor, is approved for RET fusion-positive (RET+) advanced/metastatic non-small cell lung cancer (NSCLC). RET-directed therapy has yet to be examined in patients (pts) with stage IB-IIIA RET+ NSCLC, where recurrence rates after definitive therapy remain high, and no adjuvant targeted therapy is approved. Here, we report the efficacy and safety of selpercatinib vs placebo in this population.
Methods:
LIBRETTO-432 (NCT04819100) is a placebo-controlled, double-blind, phase 3 randomized (1:1) trial of selpercatinib 160mg BID vs placebo for up to 3 years in pts with stage IB-IIIA RET+ NSCLC after definitive locoregional treatment. Primary endpoint was investigator-assessed event-free survival (EFS) in stage II-IIIA pts. Secondary endpoints were investigator-assessed EFS in all randomized pts (overall population, stage IB-IIIA), EFS by blinded independent central review (BICR), overall survival and safety. Crossover from placebo to selpercatinib was allowed upon disease recurrence.
Results:
In total, 151 pts were randomized (selpercatinib n=75; placebo n=76) and baseline characteristics were balanced across treatment arms. Median follow-up was 24 months for selpercatinib and 27 months for placebo. At the preplanned efficacy analysis, selpercatinib demonstrated significantly improved EFS in pts with stage II-IIIA disease (n=109), HR 0.172 (95% CI: 0.058, 0.509; p=0.0003). The median EFS was not reached for selpercatinib vs 31.8 months for placebo (4 vs 19 EFS events, respectively). EFS by BICR, HR=0.125 (95% CI: 0.028, 0.552; p=0.0011), was consistent with investigator-assessed EFS. The 2-year EFS rate was 91.5% for selpercatinib vs 61.1% for placebo. In the overall population (n=151), error-controlled EFS HR was 0.165 (95% CI: 0.056, 0.485; p=0.0002), and median EFS was not reached on either treatment arm. Adverse events (AEs) with selpercatinib were comparable to those reported in metastatic RET + NSCLC. The most common AEs were increased ALT/AST. Only 3 deaths were observed, all occurred in the placebo arm due to the study disease. No pts died during assigned study treatment.
Conclusions:
Selpercatinib achieved a statistically significant and clinically meaningful improvement in event-free survival compared to placebo in patients with early-stage RET+ NSCLC. These data add to the body of evidence for targeted therapy, including EGFR and ALK inhibitors, in the adjuvant NSCLC setting and underscore the importance of comprehensive genomic testing at diagnosis of NSCLC across disease stages to inform optimal therapeutic decision-making.
Citation
J Clin Oncol 44, 2026 (suppl 17; abstr LBA3)
Authors
Jonathan W. Goldman
Xuening Yang
Maximilian Hochmair
Lin Wu
Hye Ryun Kim
Luis G. Paz-Ares
Damian T. Rieke
Melissa L. Johnson
James Chih Hsin Yang
Masahiro Tsuboi
Benjamin Besse
Nivedita Sharma
Patricia H. Maeda
Patrick Peterson
Bente Frimodt-Moller
Yi Yang
Alexander E. Drilon
Yi-Long Wu
Associated Organizations
University of California Los Angeles, Los Angeles, CA, Guangdong Lung Cancer Institute, Guangdong Provincial Key Laboratory of Translational Medicine in Lung Cancer, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, China, Karl Landsteiner Institute of Lung Research and Pulmonary Oncology, Klinik Floridsdorf, Vienna, Austria; Department of Respiratory and Critical Care Medicine, Klinik Floridsdorf, Vienna Healthcare Group, Vienna, Austria, The Department of Thoracic Medical Oncology, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China, Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center; Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul, South Korea, Department of Medical Oncology, Hospital 12 de Octubre, Madrid, Spain.
Johnathan Goldman ASCO 2026 LBA3