'Striking' Responses in Pediatric Solid Tumors With Entrectinib
May 16, 2019
The investigational oral therapy entrectinib (Genentech/Roche) produced "striking, rapid, and durable" objective responses in children with recurrent/refractory central nervous system (CNS) and solid tumors harboring a range of target gene fusions, said Giles Robinson, MD, pediatric neuro-oncologist, St Jude Children's Research Hospital, Memphis, Tennessee.
The median age of these patients was 7 years old.
Robinson discussed "very promising" phase 1/2 study results with entrectinib with reporters during a press-cast that precedes presentation of the trial at the upcoming American Society of Clinical Oncology (ASCO) 2019 meeting in Chicago, Illinois.
During the press-cast, he showed scans from four study patients with high-grade gliomas, which are "universally fatal."
"It gives me great pleasure as a pediatric brain tumor doctor to show you intracranial responses to this medicine," he said.
"You can watch these tumors basically disappear or at least reduce significantly in size," he observed while displaying a series of progressive scans.
Entrectinib is an oral inhibitor of tropomyosin receptor kinase (TRK), ROS1, and ALK tyrosine kinases, which penetrate the central nervous system (CNS).
It's been established in the last few years, said Robinson, that these fusions act as "drivers" in some cancers, generating proteins that are "locked in the on position" and continuously drive tumor cell proliferation.
In the trial, responses to entrectinib were seen in 12 of the 28 evaluable patients. The 12 responses were among patients who had fusions in NTRK1/2/3, ROS1, or ALK genes (11 patients) or an ALK mutation (one patient). No responses were seen in tumors lacking aberrations in target fusions, a key insight that has led investigators to proceed in only enroling new patients with those fusions.
Median duration of therapy for confirmed fusion-positive responders was 10.5 months (3.8 to 17.7 months), and median time to response was 1.9 months (1 to 1.9 months).
The variety of solid tumors that responded, which included high-grade gliomas, three types of sarcoma, as well as a CNS embryonal tumor and a melanoma, is a source of satisfaction, suggested an expert.
The results are "yet another example of tumor-agnostic precision medicine therapy," said Monica Bertagnolli, MD, Dana-Farber Cancer Institute, Boston, Massachusetts, and ASCO president. She hopes that eventual final results will reflect what has been seen in this early study.
The variety of targetable tumors was thrilling for investigator Robinson.
"What got us really excited as pediatric oncologists was that a variety of pediatric cancers harbor these fusions and mutations," he said.
But there is more good news: the list of potentially treatable tumors is growing as investigators do next generation sequencing outside the trial in a widening number of cancers.
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