Formal discussant of the study on BLU-667, Alexander Drilon, MD, Clinical Director, Early Drug Development Service at Memorial Sloan Kettering Cancer Center, New York, was enthusiastic about these early results. “We’ve known about RET for more than 30 years. To date, no targeted therapy has been approved for this molecular target. Previously available multikinase agents were ‘dirty,’ with much off-target activity. These drugs were rationally designed to inhibit RET and are much ‘cleaner’ than many prior drugs. Multikinase inhibitors are pharmacokinetically limited in inhibiting RET, so it comes as no surprise that the activity of targeted therapy with prior agents is relatively modest,” Dr. Drilon said.
“BLU-667 is active in lung and thyroid cancers, in tyrosine kinase inhibitor–naive and multikinase inhibitor–pretreated patients. Many patients were previously treated with one or more multikinase inhibitors,” he said. “We saw the drug was active in one patient with brain metastases. Hopefully, we will see this confirmed in the future with more patients.”
‘More Tolerable Than Multikinase Inhibitors’
“Further testing will clarify the true objective response rate of BLU-667, but looking at this early datacut alone, response rates are a preliminary tie between multikinase inhibitors and BLU-667, and we don’t have progression-free survival. Stay tuned for the central nervous system activity of this drug. Hands down, however, BLU-667 is more tolerable than multikinase inhibitors,” he commented.
When asked whether older drugs should retire, Dr. Drilon said no. “But they probably shouldn’t be given first if there is access to a more selective drug,” he added, as he believes that BLU-667 represents a promising therapy that has the potential to change how we treat patients with RET-altered cancers. ■
DISCLOSURE: Dr. Drilon is on the advisory boards of Blueprint Medicines, Loxo Oncology, Ignyta, Helsinn, and Exelixis, for which he has received honoraria.
A first-in-human study provides proof of concept that a novel oral agent targeted to RET genetic alterations is safe and active in RET-driven cancers. The agent, called BLU-667, achieved durable disease control in patients with lung and thyroid cancers harboring the RET oncogene, according to the...