Entrectinib

Indication. Entrectinib is indicated for adult and pediatric patients with solid tumors and an NTRK gene fusion without a known acquired resistance variant; with disease that is metastatic or where surgical resection is likely to result in severe morbidity; and who have disease progression after treatment or have no satisfactory standard therapy.

Evidence. Five multicenter single-arm clinical trials evaluated the efficacy of entrectinib in patients with NTRK-positive tumors. Three of these trials evaluated a total of 54 adult patients who received entrectinib at various doses and schedules. Two of these trials evaluated a total of 33 pediatric patients.[1,2][Level of evidence C3]

Efficacy. Among the 54 adult patients, the overall response rate, as determined by independent review, was 57% (95% confidence interval [CI], 43%–71%). The median follow-up was 15 months.[1] Among the 33 pediatric patients, the objective response rate was 70% (95% CI, 51%–84%), and the median duration of response was 25.4 months (95% CI, 14.3–not evaluable). The median follow-up was not defined.[2]

Identification of biomarker. Identification of positive NTRK gene fusion status was determined at local laboratories or a central laboratory using nucleic acid-based tests prior to enrollment. Not all NTRK variants are gene fusions. Entrectinib has not shown clinical efficacy in patients with nonfusion NTRK variants..