Efficacy
Adult patients
The efficacy of entrectinib was assessed in adult patients with solid tumours and confirmed NTRK gene fusion enrolled in one of three clinical trials (ALKA, STARTRK-1 and STARTRK-2). The primary efficacy endpoints were objective response rate (ORR) and duration of response (DOR) as evaluated by Blinded Independent Central Review (BICR) according to RECIST v1.1 and are summarized in the table below [extracted from 1].
Overall efficacy by BICR in adults with NTRK gene fusion-positive solid tumours
(Source: Entrectinib EMA Summary of medicinal Product Characteristics. 2022)Efficacy endpoint |
n=150 |
|
Objective Response Rate - Number of Responses - ORR% (95% CI) Complete Response, n (%) Partial Response, n (%) |
92/150 61.3% (53.0, 69.2) 25 (16.7%) 67 (44.7%) |
|
Duration of Response* - Number (%) of patients with events - Median, months (95% CI) 6-month durable response % (95% CI) 9-month durable response % (95% CI) 12-month durable response % (95% CI) |
50/92 (54.3%) 20 (13.2, 31.1) 83% (75, 91) 77% (68,86) 66% (56,76) |
An overview of the ORR and Duration of Response (DOR) observed in the pooled data analysis from the three clinical trials, is shown in the table below [extracted from 1]. It should be noted however that considering the rarity of TRK fusion-positive cancers efficacy estimates per tumour type may not necessarily reflect the expected response in a specific tumour type.
Intracranial (IC) response
Across the three trials, 22 adults had CNS metastasis at baselined including 13 with measurable lesions. Assessment of IC according to RECIST v1.1 reported for 9 out of these 13 patients (3 CR and 6 PR), found an ORR of 69.2% (95% CI: 38.6, 90.9) and median DOR of 17.2 (7.4, NE). Five of these 13 patients had received intracranial radiotherapy to the brain within 2 months prior to starting entrectinib treatment.
Primary CNS tumours
A total of 12 adult patients with CNS primary tumours were treated with entrectinib in the three registration trials, with a minimum of 12 months of follow-up. One out of the 12 adult patients had an objective response, according to RANO.
Efficacy in paediatric patients
The efficacy of entrectinib in paediatric patients 12 years and older harbouring NTRK gene fusion was based on extrapolation of data from the ALKA, STARTRK-1, STARTRK-2 and STARTRK-NG clinical trials. The best overall response in 5 paediatric patients (all were less than 12 years of age and had more than 6 months of follow up; 3 patients had solid tumours and 2 patients had primary CNS tumours) showed 2 complete responses (epithelioid glioblastoma and infantile fibrosarcoma) and 3 partial responses (high-grade glioma, infantile fibrosarcoma and metastatic melanoma).
References
- ROZLYTREK (entrectinib), EMA Summary of medicinal Product Characteristics. 2022.
- Demetri GD, De Braud F, Drilon A et al. Updated Integrated Analysis of the Efficacy and Safety of Entrectinib in Patients With NTRK Fusion-Positive Solid Tumors. Clin Cancer Res. 2022 Apr 1;28(7):1302-1312.