- The FDA has granted accelerated approval for entrectinib (Rozlytrek) to treat tumors positive for fusion in the neurotrophic tyrosine receptor kinase (NTRK) gene in patients aged ≥12 years.
- Indicated for metastatic or unresectable disease with posttreatment progression or no therapeutic options.
- Entrectinib was also approved for the treatment of adults with metastatic, ROS1+ NSCLC.
Why this matters
- Agents previously approved to target a genetic defect rather than tumor type include larotrectinib (Vitrakvi, for NTRK+ tumors) and pembrolizumab (Keytruda).
- Prescribing information is available here.
- Approval was based on a pooled analysis of data from 4 multicenter, single-arm, open-label trials: ALKA-372-001, STARTRK-1, STARTRK-2, and STARTRK-NG.
- NTRK+ solid tumors: 54 patients with locally advanced (4%) or metastatic (96%) disease.
- 10 tumor types: sarcoma; NSCLC; salivary gland, breast, thyroid, colorectal, neuroendocrine, pancreatic, and gynecologic cancers; and cholangiocarcinoma.
- ROS1+ NSCLC: 53 patients (94% adenocarcinoma); 94% with metastatic disease and 43% with central nervous system (CNS) metastases.
- Funding: Genentech.
- NTRK+ solid tumors: overall response rate (ORR), 57% (complete response, 7.4%; partial response, 50%).
- Duration of response (DOR), ≥6, 9, and 12 months: 68%, 61%, and 45%, respectively.
- ORR highest with salivary cancer (86%), breast cancer (83%), and NSCLC (70%).
- ROS1+ NSCLC: ORR, 78% (complete response, 6%; partial response, 73%).
- DOR, ≥9, 12, and 18 months: 70%, 55%, and 30%, respectively.
- 5/7 with measurable CNS metastases showed intracranial response.
- Serious adverse events may include congestive heart failure; CNS effects including cognitive impairment, mood disorders, dizziness; skeletal fractures, hepatotoxicity, hyperuricemia, QT prolongation, and vision disorders.