Invited discussant Juan W. Valle, MD, of the University of Manchester/The Christie, United Kingdom, reiterated the 50% response rate, the median progression-free survival of 7.1 months, and the median overall survival of 16.0 months achieved with entrectinib in patients who had gastrointestinal cancers with NTRK fusions included in the three key trials of patients enriched for this molecular alteration. “These responses were durable, with a median duration of response of 12.9 months, largely driven by the 15.1-month duration in patients with colorectal cancer,” he noted.
Although the findings are promising, Dr. Valle reminded listeners of the “immortal time bias” in the study, which required all patients have at least 6 months of follow-up. “More mature data are awaited,” he said.
Juan W. Valle, MD
NTRK Gene Fusions: Rare in Pancreaticobiliary Cancers
Dr. Valle also commented on the value of the two-step diagnostic method used by Dr. Demols and colleagues from Belgium in biobanked specimens of patients with biliary tract and pancreatic cancers. “They initially undertook immunohistochemistry with a pan-NTRK monoclonal antibody, describing the intensity of staining as well as its pattern and localization,” he said. “In patients deemed positive, they then went to RNA-based next-generation sequencing with the Oncomine Focus assay to identify NTRK gene fusions.”
“They found only one patient with a gene fusion in the biliary tract cancer cohort, for a 0.67% prevalence. No patient with pancreatic cancer had a gene fusion,” commented Dr. Valle.
From these data, it can be assumed that NTRK gene fusions are rare in pancreaticobiliary cancers, and a two-step diagnostic approach can preselect patients suitable for a next-generation sequencing assay, Dr. Valle concluded. “In the study presented by Dr. Patel, we saw that the therapeutic implications make this an important diagnosis,” he said.
DISCLOSURE: Dr. Valle has received honoraria from Ipsen; has served as a consultant or advisor to Agios, AstraZeneca, Debiopharm Group, Delcath Systems, Genoscience Pharma, Imaging Equipment Limited (AAA), Incyte, Ipsen, Keocyt, Merck, Mundipharma EDO, Novartis, NuCana BioMed, PCI Biotech, Pfizer, Pieris Pharmaceuticals, QED, Servier, and Wren Laboratories; has participated in a speakers bureau for Imaging Equipment Limited, Ipsen, Novartis, and NuCana; has received institutional research funding from Novartis; and has been reimbursed for travel, accommodations, or other expenses by Celgene, NuCana, and Pfizer.
Although NTRK gene fusions occur in less than 5% of gastrointestinal cancers, it looks like they can be targeted successfully with NTRK inhibitors. In a pooled analysis of three clinical trials, 50% of such patients responded to entrectinib, in an updated analysis presented during the 2020 virtual...