KEY TAKEAWAYS
- An integrated analysis of three phase I or II clinical trials (ALKA-372-001, STARTRK-1, and STARTRK-2) of entrectinib, a ROS1 tyrosine kinase inhibitor, in non-small-cell lung cancer (NSCLC) with ROS1 fusion-positive genetic changes was reported in this study.
- The study’s primary aim was to assess the efficacy and safety of entrectinib in adults with locally advanced or metastatic ROS1 fusion-positive NSCLC, with or without CNS tumors.
- The participants in the study received entrectinib orally at a dosage of 600 mg once daily. The ORR and DoR were measured as the primary endpoints.
- Among the 161 patients followed up for at least 6 months, the ORR was 67.1%, with a 12-month DoR rate of 63% and a median DoR of 15.7 months. The 12-month PFS rate was 55%, and the 12-month OS rate was 81%.
- The average length of treatment in the study was approximately 10.7 months (IQR: 6.4–17.7). The safety profile of entrectinib remained consistent with the previous analysis, and no new safety signals were identified.
- The updated analysis demonstrates that entrectinib continues to show significant clinical benefit in patients with ROS1 fusion-positive NSCLC, including those with CNS metastases.
Non-small-cell lung cancer (NSCLC) is caused by genetic changes in the tyrosine receptor kinase ROS proto-oncogene 1 (ROS1). Researchers reported the results of an updated integrated study of three phase I or II clinical trials (ALKA-372-001, STARTRK-1, and STARTRK-2) of entrectinib, a ROS1 tyrosine kinase inhibitor, in ROS1 fusion-positive NSCLC. Adults with locally advanced or metastatic ROS1 fusion-positive NSCLC, with or without CNS tumors, who took entrectinib 600 mg orally once a day were used to measure how well it worked. The two most essential endpoints were objective reaction rate (ORR), measured by a blinded, independent central review, and duration of response (DoR). The secondary end goals were progression-free survival (PFS), overall survival (OS), intracranial ORR, intracranial DoR, intracranial PFS, and safety.
The investigators evaluated 161 people who had been followed up on for at ≥ 6 months. The average length of treatment was about 10.7 months (IQR: 6.4–17.7). The ORR was 67.1% (n = 108, 95% CI: 59.3–74.3), and the effects lasted (12-month DoR rate: 63%, median DoR: 15.7 months). The 12-month PFS rate was 55% (the median PFS was 15.7 months), and the 12-month OS rate was 81% (the median OS could not be estimated). In 24 patients with detectable CNS tumors at baseline, a blinded independent central review showed that the intracranial ORR was 79.2% (n = 19; 95% CI, 57.9 to 92.9), the median intracranial PFS was 12.0 months (95% CI, 6.2 to 19.3), and the median intracranial DoR was 12.9 months (55% 12-month rate). In this updated analysis, the safety profile was the same as in the first analysis, and no new safety signs were found. Entrectinib continued to show a high level of clinical improvement for patients with ROS1 fusion-positive NSCLC, including patients with CNS metastases.
Source: https://pubmed.ncbi.nlm.nih.gov/33646820/
Clinical Trial: http://clinicaltrials.gov/show/NCT02097810
Dziadziuszko R, Krebs MG, De Braud F, Siena S, Drilon A, Doebele RC, Patel MR, Cho BC, Liu SV, Ahn MJ, Chiu CH, Farago AF, Lin CC, Karapetis CS, Li YC, Day BM, Chen D, Wilson TR, Barlesi F. Updated Integrated Analysis of the Efficacy and Safety of Entrectinib in Locally Advanced or Metastatic ROS1 Fusion-Positive Non-Small-Cell Lung Cancer. J Clin Oncol. 2021 Apr 10;39(11):1253-1263. doi: 10.1200/JCO.20.03025. Epub 2021 Mar 1. PMID: 33646820; PMCID: PMC8078299.
