TRK Inhibitors for Advanced Solid Tumors: Next Steps in Research


David S. Hong, MD, of The University of Texas MD Anderson Cancer Center, shares his enthusiasm for ongoing research efforts to optimize treatment for patients with advanced solid tumors who harbor NTRK gene fusions.

David S. Hong, MD: The next steps in understanding and NTRK are the mechanism resistances. We already have a clear idea of what the mechanism resistances are with larotrectinib and entrectinib: Patients develop what are called solvent front and gatekeeper and what are called DFG mutations that can confer resistance to the first generation of drugs. There’s an ongoing study that several colleagues around the world and I are running, which is also developed by Loxo Oncology, Inc in collaboration with Bayer AG, the trial with the molecule selitrectinib is ongoing. We are seeing robust responses in patients who have developed resistance to the first-generation molecules.

In many ways, this disease is analogous in the context of solid tumors to another disease, such as CML [chronic myelogenous leukemia], which was the first disease that we were able to target with a targeted-therapy imatinib. For patients with chronic CML who get imatinib and the next generation of molecules down the line, their life span essentially is normalized. They have the normal life span of a normal person. We’re not there with NTRK fusion–positive cancer patients, but as we become more cognizant, more patients are screened molecularly, and we identify these patients earlier, the disease course and eventually the survival course of these patients who develop solid tumor cancers and who have NTRK fusions may be similar to what we are seeing now with CML.

Transcript edited for clarity.

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