Dr. Strickler on Therapies for Rare Variants of Relapsed/Refractory CRC

John Strickler, MD, assistant professor of medicine at Duke University School of Medicine, gastrointestinal oncologist, Duke Cancer Institute, discusses therapies for rare variants of relapsed/refractory colorectal cancer (CRC).

Most of the emerging therapies and targets in patients with relapsed/refractory CRC have been in the rare genetic alterations discovered through comprehensive molecular profiling, Strickler says. Most recently, patients whose tumors express microsatellite instability—high and mismatch repair deficiency have been shown to respond to single-agent and combination checkpoint inhibitors, such as pembrolizumab (Keytruda) and the combination of nivolumab (Opdivo) and ipilimumab (Yervoy).

In addition, genomic targets that have recently been evaluated include BRAF mutations, which Strickler says researchers have known about for a while. When patients come into the clinic with BRAF-mutated CRC, there are a number of targeted therapies being evaluated that they can be matched with. For patients with NTRK-positive fusions, there was recently a tumor agnostic FDA approval for larotrectinib (Vitrakvi), an NTRK inhibitor that has been shown to be quite active in those patients. Strickler notes that like the other aforementioned patient populations, this genomic variant is very rare.