Updated results confirm efficacy and safety of entrectinib in patients with NTRK fusion-positive NSCLC

In an integrated analysis of 3 trials, entrectinib was associated with deep and durable responses in patients with NTRK fusion-positive (-fp) non-small cell lung cancer (NSCLC), including those with baseline CNS metastases.

Fusions involving the NTRK gene family lead to the expression of chimeric rearrangements in tropomyosin receptor kinases (TRKs) with constitutively active kinase function. NTRK gene fusions act as oncogenic drivers and are potential therapeutic targets across a broad range of tumour types, including NSCLC [1]. Entrectinib is a potent inhibitor of TRK proteins that is specifically designed to have systemic activity and crosses the blood-brain barrier. Entrectinib has shown strong efficacy in patients with NTRK-fp solid tumours in the phase 1/2 ALKA-372-001 (EudraCT 2012-000148-88), STARTRK-1 (NCT02097810), and STARTRK-2 (NCT02568267) clinical trials [2,3]. An integrated analysis of the NTRK-fp NSCLC patients in these 3 trials was presented by Prof. Byoung Chul Cho (Yonsei Cancer Center Seoul, South Korea) [4,5].

At data cut-off, 22 patients with NTRK-fp NSCLC were included in the efficacy-evaluable population; 13 patients (59.1%) had CNS metastases at baseline, median age was 60.5 years, 9 patients had ≥2 prior systemic therapies. Follow-up was ≥13 months since the start of treatment; median duration of follow-up was 19.2 months.

The confirmed overall response rate (ORR) was 63.6% (53.8% in patients with baseline CNS metastases; 77.8% in patients without baseline CNS metastases). Complete response was observed in 7.7% of patients with CNS metastases and in 11.1% of patients with no baseline CNS metastases. The median progression-free survival was 14.9 months, median overall survival was not reached.

Most treatment-related adverse events were grade 1 or 2 and manageable with dose modifications. The most frequent treatment-related events were dysgeusia (46.2%), fatigue (33.3%), and increased blood creatinine (33.3%).

“This analysis confirms previously observed efficacy and safety of entrectinib in patients with NTRK-fp NSCLC, including those with baseline CNS metastases,” concluded Dr Cho. “Entrectinib is associated with deep and durable responses.”

1. Vaishnavi A, et al. Nat Med. 2013;19:1469–1472.


2. Doebele RC, et al. Lancet Oncol. 2020;21:271–281.


3. Demetri GD, et al. Clin Cancer Res. 2022;28:1302–1312.


4. Drilon A, et al. Abstract 543P. ESMO Virtual Congress 2020, 19–21 September.


5. Cho BC, et al. Updated efficacy and safety of entrectinib in patients (pts) with NTRK fusion-positive (NTRK-fp) NSCLC. Abstract 110P. ELCC 2022 Virtual Meeting, 30 March–02 April.

 

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Posted on 25 May, 2022