Entrectinib Shrank NTRK Fusion-Positive Solid Tumors
More than half of patients with central nervous system metastases responded to the drug.
|The following article features coverage from the European Society for Medical Oncology (ESMO) 2018 meeting. Click here to read more of Cancer Therapy Advisor's conference coverage.|
The TRKA/B/C and ROS1 inhibitor entrectinib induced clinically meaningful and durable responses in patients with NTRK-fusion-positive solid tumors, a type of tumor with no approved therapies at this time.
Results of a pooled analysis presented at the 2018 ESMO Congress in Munich, Germany, showed that nearly 60% of treated patients responded to entrectinib.
The analysis included data from 3 phase 1/2 trials: ALKA, STARTRK-1, and STARTRK-2. These trials included patients with locally advanced or metastatic NTRK fusion-positive tumors enrolled across 15 countries. Tumors were assessed for response at 4 weeks and then every 8 weeks thereafter.
Efficacy was evaluated in 54 patients, including some with baseline central nervous system (CNS) metastases. After 15.5 months of follow-up, the blinded independent committee review-assessed overall response rate was 57.4%, including 7.4% of patients who achieved complete response. Responses were seen in all 10 tumor types representing more than 19 histopathologies. The median duration of response was almost 1 year (10.4 months).
Median progression-free survival was 11.2 months, with a median overall survival of 20.9 months.
The researchers looked at outcomes among patients with or without CNS metastases. Entrectinib shrank tumors in 54.5% of patients with CNS metastases, with more than one quarter demonstrating a complete response. The median progression-free survival was 12 months in patients without metastases (42 patients) compared with 7.7 months for those with brain metastases (12 patients).
Safety was evaluated in 355 patients from the three clinical trials. The most common adverse events were grade 1/2 and were successfully managed with a dose reduction in 27.3% of patients. Only 4% of patients had to discontinue treatment do to treatment-related adverse events.
Entrectinib has been granted a breakthrough therapy designation by the US Food and Drug Administration for the treatment of NTRK fusion-positive, locally advanced, or metastatic solid tumors in adult and pediatric patients who have either progressed following prior therapies or have no acceptable standard therapies.
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- Demetri GD. Efficacy and safety of entrectinib in patients with NTRK fusion-positive (NTRK-fp) tumors: pooled analysis of STARTRK-2, STARTRK-1, and ALKA-372-001. Abstract presented at: the ESMO 2018 Congress; Munich, Germany: October 19-23, 2018. Abstract LBA17.