This has been studied in a few trials—initially with vemurafenib (Zelboraf)—which has shown a good response rate of about 42% in a phase II study. The combination of BRAF and MEK inhibitors showed good response rates and tolerability, and has gained FDA approval—just like in melanoma. Response rates were not as good as EGFR
-mutated lung cancer when treated with EGFR inhibitors.
You mentioned entrectinib. Could you share some insight on that agent?
Entrectinib is a new oral tyrosine kinase inhibitor that targets the TRK signal, but is also known to have responses to ALK, as well as ROS1. The initial phase I study revealed that there were complete responses in all of the 3 patients with TRK
mutations, and a 70% response rate in ROS1
-mutated patients, and it is being studied as a global basket trial at 134 centers. [This study] is looking at responsiveness of entrectinib in several cancers that could harbor TRK mutations.
MSI is largely associated with colorectal cancer. What is its role as a target in lung cancer?
MSI is starting to gain more attention, especially with the recent evidence of MSI-high (MSI-H) tumors responding well to immunotherapy. Pembrolizumab (Keytruda) is approved in all of the solid tumors that exhibit MSI-H. Hence, MSI is a good marker, as well, although the instance of MSI in NSCLC is 0.8%, based on the limited data that we have. This was a study involving 480 patients with adenocarcinomas. Certainly, as we subtype more lung cancers, we may better understand the instances of MSI-H tumors in lung cancer.