Entrectinib in Advanced or Metastatic NTRK Fusion–Positive Solid Tumors

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As reported in The Lancet Oncology by George D. Demetri, MD, and colleagues, integrated analysis of three phase I/II trials has shown high levels of activity of the tropomyosin receptor kinase (TRK) inhibitor entrectinib in advanced NTRK fusion–positive solid tumors. This analysis supported the August 2019 U.S. Food and Drug Administration approval of entrectinib in this setting.

George D. Demetri, MD

George D. Demetri, MD

Study Details

The integrated efficacy analysis included 54 efficacy-evaluable adult patients with advanced or metastatic NTRK fusion–positive solid tumors representing 10 tumor types and 19 different histologies enrolled in the single-arm ALKA-372-001, STARTRK-1, and STARTRK-2 trials. Patients received entrectinib at a dose of at least 600 mg once per day.

Patients could have received prior anticancer therapy, except for prior TRK inhibitor treatment. The most common tumor types included in the analysis were sarcoma (24%), non–small cell lung cancer (19%), and mammary analog secretory carcinoma of the salivary gland (13%).


Median follow-up was 12.9 months. Objective response on blinded independent central review was achieved in 31 patients (57%, 95% confidence interval [CI] = 43.2%–70.8%), with complete response observed in 4 (7%). Responses were observed in all tumor types.

Stable disease was observed in an additional nine patients (17%). Median duration of response was 10 months (95% CI = 7.1 months–not estimable). Median progression-free survival was 11 months (95% CI = 8.0–14.9 months).


  • Objective response on blinded independent central review was achieved in 31 patients, with complete response observed in 4.
  • Responses were observed in all tumor types.

Adverse Events

The most common grade 3 or 4 treatment-related adverse events among 68 patients with NTRK fusion–positive disease who received at least one dose of entrectinib in the three studies were anemia (12%), increased weight (10%), and fatigue (7%). Serious treatment-related adverse events were reported in 10% of patients, with the most common being nervous system disorders (4%).

The investigators concluded, “Entrectinib induced durable and clinically meaningful responses in patients with NTRK fusion–positive solid tumors and was well tolerated with a manageable safety profile. These results show that entrectinib is a safe and active treatment option for patients with NTRK fusion–positive solid tumors. These data highlight the need to routinely test for NTRK fusions to broaden the therapeutic options available for patients with NTRK fusion–positive solid tumors.”

Dr. Demetri, of Dana-Farber Cancer Institute and Ludwig Center, Harvard Medical School, is the corresponding author for The Lancet Oncology article.

Disclosure: The study was funded by Ignyta/F. Hoffmann-La Roche. For full disclosures of the study authors, visit

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