Robert Doebele, MD, PhD
Roy S. Herbst, MD, PhD
Discussant of the LIBRETTO-001 trial, Robert Doebele, MD, PhD, of the University of Colorado Anschutz Medical Campus in Aurora, Colorado, was enthusiastic about the response rates reported in this preliminary trial. “Older trials of multikinase inhibitors have shown response rates in the range of 25% and a median progression-free survival in the range of 2 to 3 months in patients with RET fusion–positive NSCLC. Here, we see a 68% response rate and a median progression-free survival of 18.4 months,” Dr. Doebele noted.
“Mechanisms of resistance to selpercatinib will likely differ from those of older multikinase inibitors and will need further study,” he added.
Roy S. Herbst, MD, PhD, of the Yale Cancer Center, New Haven, Connecticut, was also encouraged by these results from LIBRETTO-001. “These data certainly exceeded expectations. The high response rates in pretreated and untreated patients with impressive durability suggest this drug will quickly move into front-line therapy for lung cancer. The key is to be sure that all next-generation sequencing and other platforms routinely test for RET fusions to pick up this target, which occurs only on the order of a few percent.” ■
DISCLOSURE: Dr. Doebele has served as a consultant/advisor for AstraZeneca, Bayer Healthcare, Genentech, Rain Therapeutics, Roche, and Takeda and owns stock in Rain Therapeutics. Dr. Herbst is a consultant for AbbVie Pharmaceuticals, Armo Biosciences, AstraZeneca, Biodesix, Bristol-Myers Squibb, Eli Lilly, EMD Serrano, Genentech/Roche, Genmab, Halozyme, Heat Biologics, Infinity Pharmaceuticals, Loxo Oncology, Merck, Nektar, Neon Therapeutics, NextCure, Novartis, Pfizer, Sanofi, Seattle Genetics, Shire PLC, Spectrum Pharmaceuticals, Symphogen, Tesaro, and Tocagen; has received research support from AstraZeneca, Eli Lilly, and Merck; and is a member of the Board of Directors (nonexecutive/independent) for Junshi Biosciences.
Selpercatinib (LOXO-292), a RET kinase inhibitor, demonstrated antitumor activity in the lungs and brain and durable responses with acceptable tolerability in patients with RET fusion–positive non–small cell lung cancer (NSCLC), according to an updated analysis of the LIBRETTO-001 registration...