Brief report: Updated efficacy and safety data from an integrated analysis of entrectinib in locally advanced/metastatic ROS1 fusion-positive non–small-cell lung cancer Journal Article
| Authors: | Fan, Y.; Drilon, A.; Chiu, C. H.; Loong, H. H. F.; Siena, S.; Krzakowski, M.; Dziadziuszko, R.; Zeuner, H.; Xue, C.; Krebs, M. G. |
| Article Title: | Brief report: Updated efficacy and safety data from an integrated analysis of entrectinib in locally advanced/metastatic ROS1 fusion-positive non–small-cell lung cancer |
| Abstract: | • Genetic alterations in ROS1 can lead to the expression of oncogenic fusion proteins in multiple tumor types, including in 1% to 2% of non–small-cell lung cancer (NSCLC) cases. Approximately 40% of patients with ROS1 fusion-positive NSCLC have baseline central nervous system (CNS) metastases, indicating the need for a treatment with CNS activity. Entrectinib, a potent ROS1 tyrosine kinase inhibitor with activity in the CNS, has previously demonstrated overall and intracranial efficacy, and a manageable safety profile, in patients with ROS1 fusion-positive NSCLC. • In this updated analysis with 4 additional patients and longer follow-up, the objective response rate (ORR) in the efficacy-evaluable population (N = 172) was 67%; median duration of response (DoR) was 20.4 months, and median progression-free survival was 16.8 months. In 51 patients with baseline CNS metastases, intracranial ORR was 49% and median intracranial DoR was 12.9 months. In a subgroup analysis in patients who had not received any prior systemic therapy in the metastatic setting, ORR was similar to that in the efficacy-evaluable population, but median DoR was numerically longer at 35.6 months. Most treatment-related adverse events were grade 1 to 2 and nonserious. • These data reinforce previous findings on the use of entrectinib for the treatment of patients with ROS1 fusion-positive NSCLC, and support current guidelines that recommend entrectinib as a first-line treatment option for these patients, including those with baseline CNS metastases. © 2023 The Authors |
| Keywords: | controlled study; unclassified drug; oncoprotein; major clinical study; overall survival; genetics; proto-oncogene proteins; case report; advanced cancer; drug efficacy; drug safety; side effect; brain radiation; follow up; progression free survival; protein kinase inhibitor; carcinoma, non-small-cell lung; lung neoplasms; pathology; protein tyrosine kinase; dizziness; dyspnea; protein kinase inhibitors; lung tumor; lung metastasis; fusion gene; protein-tyrosine kinases; tyrosine kinase inhibitor; dysgeusia; non small cell lung cancer; nsclc; central nervous system metastasis; benzamide derivative; benzamides; indazoles; oncological parameters; first-line treatment; response evaluation criteria in solid tumors; objective response rate; humans; human; article; entrectinib; ecog performance status; body weight gain; treatment response time; ros1 protein, human; indazole derivative; proto oncogene protein; intracranial efficacy; protein ros proto oncogene 1 |
| Journal Title: | Clinical Lung Cancer |
| Volume: | 25 |
| Issue: | 2 |
| ISSN: | 1525-7304 |
| Publisher: | Elsevier Inc. |
| Date Published: | 2024-03-01 |
| Start Page: | e81 |
| End Page: | e86.e4 |
| Language: | English |
| DOI: | 10.1016/j.cllc.2023.12.001 |
| PUBMED: | 38245456 |
| PROVIDER: | scopus |
| PMCID: | PMC11733145 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PDF -- Source: Scopus |
