Concerning Kinases: Therapeutic Considerations for RET Rearranged NSCLC

Dr. Sands:
Welcome to Project Oncology on ReachMD. I’m Dr. Jacob Sands, and on this episode, Dr. Ross Camidge, the Director of the Thoracic Oncology Clinical and Clinical Research Programs at the University of Colorado, joins us to discuss clinical considerations for RET-rearranged non-small cell lung cancer. Let’s hear from him now.

Dr. Camidge:
If you’re diagnosed with RET rearranged advanced non-small cell lung cancer, as of 2020, you have two targeted therapy options. Selpercatinib and pralsetinib are both RET tyrosine kinase inhibitors, and both have got a really very high response rate - 60-70%, if not more; are pills, and I think would be the preferred option rather than giving the patient standard chemotherapy or chemoimmunotherapy. Now when you have two different pill options, of course everyone is asked which is the best one, and the answer is there probably isn’t one best one for everybody. They have somewhat different side effect profiles, and that allows you to have the option of trying one and if it doesn’t work, you have the other one as a backup. They have slightly different side effect profiles; so for example, selpercatinib can in some patients produce a sort of allergic-type reaction. It’s relatively rare, but it can happen. Pralsetinib can produce some myelosuppression, so even though it’s a pill and it’s not chemotherapy, you can have people who will drop their hemoglobin, for example. In general, most of these pills are relatively well-tolerated, and what I usually do is I start somebody on the pill, I’ll probably see them about two weeks later and check both their physical and their laboratory signs of any toxicity, and if they’re doing okay, I’d probably do the first scan about four weeks after that, so about six weeks after they started.

In general, these drugs are good. They’re highly effective. We’re not 100% clear in terms of how effective they are in the brain. There is some soft data with pralsetinib that has got activity in the brain. There is some soft data with selpercatinib, although it’s a slightly larger data set, that it has activity in the brain. I think for a patient with asymptomatic brain metastases, you could certainly try these agents and keep an eye on it, but I think you can’t just assume that it’s going to have equivalent of activity in the brain as in the body.

Dr. Sands:
That was Dr. Ross Camidge from the University of Colorado. And for ReachMD, I’m Dr. Jacob Sands. To revisit any part of this discussion and to access other episodes in this series, visit ReachMD.com/ Project Oncology, where you can Be Part of the Knowledge. Thanks for listening.