Larotrectinib and CNS Metastasis in TRK Fusion-Positive Tumors


The significance of recent data exploring larotrectinib, a TRK inhibitor, in a subset of patients with TRK fusion–positive tumors with CNS (central nervous system) metastasis.

David S. Hong, MD: The most recent data set we’ve presented was at our ESMO [European Society for Medical Oncology Congress] presentation by Ray McDermott, but we had also presented this similar data set in the Lancet Oncology paper. In the most recent updated data set, we had close to 175 patients on that trial. Similar to the first data set that we published in the New England Journal of Medicine, the overall response rate was incredibly similar. The overall response rate was close to 80% or 78%. The complete response rate was 33%. The progression-free survival was close to 36.8 months, the duration response had not been reached, and the median overall survival had not been reached. That confirms the incredible efficacy of particularly the larotrectinib molecule. For entrectinib, the most recent data set is not much different from the approval data set, so we don’t have a clear idea how to compare these at this time. But larotrectinib is showing really incredible efficacy that has been sustained from the beginning when we published the phase 1 data to close to 175 patients.

We know that larotrectinib and also entrectinib can cross the blood-brain barrier. The most recent data set that was presented was presented by my colleague, Dr [Alexander] Drilon from MSKCC [Memorial Sloan Kettering Cancer Center] at ASCO [American Society of Clinical Oncology Annual Meeting], about 2 years ago. In that data set, we had 24 patients with intracranial disease; 18 had primary CNS [central nervous system] tumors, and 6 had nonprimary CNS. The overall response rate in this data set was excellent in 5 of the valuable patients. For the solid tumors with brain metastases, we had a response rate of approximately 60%. In those patients who had primary CNS metastasis, the response rate was approximately 36%. That may just reflect the biology of fairly aggressive disease in the brain. Overall, if you ask a neuro-oncologist, they’ll tell you 36% response rate in patients with primary-refractory CNS tumors is pretty remarkable.

Transcript edited for clarity.

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