ASCO 2019: Entrectinib Produces Responses in Children, Adolescents With Central Nervous System Cancers


Nearly half of evaluable patients with rare central nervous system tumors, neuroblastoma, or other solid tumors had responses to entrectinib.

A novel targeted treatment was shown to demonstrate responses in children and adolescents with recurrent or refractory central nervous system (CNS) tumors, neuroblastoma, or other solid tumors, according to a study presented at the 2019 ASCO Annual Meeting in Chicago.

Entrectinib is an oral systemic medication that also penetrates the CNS to inhibit protein pathways related to mutations in NTRK1/2/3, ROS1, and ALK genes to promote cancer cell death, according to a press release about the study. This oral drug has broader activity that targets multiple mutations compared with other medications, which are only effective against 1 mutation.

In an ASCO presscast, study author Giles W. Robinson, MD, a pediatric neuro-oncologist at St. Jude Children’s Research Hospital, discussed the findings and implications for pediatric patients.

The phase 1/1B study included 29 patients between the ages of 4.9 and 20 years old, all of whom have rare CNS tumors, neuroblastoma, or other solid tumors. Approximately 12 of the 28 evaluable patients had responses to entrectinib, wherein the tumor shrank or disappeared. The 12 pediatric patients who experienced a response to therapy had fusions in NTRK1/2/3, ROS1, or ALK genes (11 patients) or an ALK mutation (1 patient), according to the results.

“Overall, entrectinib produced striking, rapid, and durable responses in all children with refractory CNS and solid tumors that actually harbored these fusions in NTRK1/2/3, ROS1, or ALK,” Dr Robinson said in the presscast. “It also produced a significant response in 1 ALK-mutated neuroblastoma patient.” Notably, no responses were seen in tumors lacking aberrations in target kinases, he added.

The recommended dose of entrectinib in children is 550 mg/m2 once daily, according to the study. Noted adverse effects included fatigue, elevated creatinine levels, dysgeusia resulting in loss of taste and, at a higher dose, incidence of pulmonary edema resulting in fluid in the lungs. Also noted was weight gain, an adverse effect not commonly found in cancer medicines. These adverse effects have resulted in dose reductions to 400 mg/m2.

“Entrectinib really is very promising,” Dr Robinson concluded. “It has very promising anti-tumor activity and progression-free survival, but in patients with target gene fusions and this is even true for patients with malignant CNS tumors.”

As a result, the trial is continuing but is now limited to patients only with target fusion.

Accrual to the clinical trial is ongoing. Investigators hope to determine long-term adverse effects and duration of response on and off therapy, according to the press release.


Robinson GW, Gajjar AJ, Gauvain KM, et al. Phase 1/1B trial to assess the activity of entrectinib in children and adolescents with recurrent or refractory solid tumors including central nervous systems (CNS) tumors. J Clin Oncol 37, 2019 (suppl; abstr 10009). Presented at: 2019 ASCO Annual Meeting. May 31-June 4, 2019. Chicago, Illinois.

Entrectinib Produces Responses in Children and Adolescents With CNS and Other Cancers That Have Specific Gene Fusions [news release]. ASCO. Accessed May 15, 2019.

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