Larotrectinib treatment for patients with TRK fusion-positive salivary gland cancers Journal Article
| Authors: | Le, X.; Baik, C.; Bauman, J.; Gilbert, J.; Brose, M. S.; Grilley-Olson, J. E.; Patil, T.; McDermott, R.; Raez, L. E.; Johnson, J. M.; Shen, L.; Tahara, M.; Ho, A. L.; Norenberg, R.; Dima, L.; Brega, N.; Drilon, A.; Hong, D. S. |
| Article Title: | Larotrectinib treatment for patients with TRK fusion-positive salivary gland cancers |
| Abstract: | Background: Larotrectinib is a first-in-class, highly selective, and central nervous system-active tropomyosin receptor kinase (TRK) inhibitor approved for the treatment of adult and pediatric patients with TRK fusion cancer. We report the efficacy and safety of larotrectinib in patients with TRK fusion-positive salivary gland cancers. Patients and Methods: Patients with TRK fusion-positive salivary gland cancer treated with larotrectinib were identified from two clinical trials (NCT02122913 and NCT02576431). Patients received larotrectinib 100 mg twice daily (BID) except for one patient who received 150 mg BID in the phase I trial. The primary endpoint was objective response rate (ORR) as assessed by the investigator using Response Evaluation Criteria in Solid Tumors version 1.1. Results: At the data cut-off (July 20, 2020), 24 patients with TRK fusion-positive salivary gland cancer had been treated. The most common histologies were secretory carcinoma (54%), adenocarcinoma (25%), and mucoepidermoid carcinoma (13%). All 24 patients had an ETV6-NTRK3 gene fusion. The ORR was 92% (95% confidence interval, 73-99). Best overall response was complete response in three (13%) patients, partial response in 19 (79%), and progressive disease in two (8%). The rate of progression-free survival at 24 months was 78% (median follow-up 30.9 months). Most treatment-related adverse events (AEs) were grade 1-2, and no patients discontinued treatment due to AEs. Conclusion: Larotrectinib demonstrated robust and durable efficacy in patients with TRK fusion-positive salivary gland tumors of various histologies, and a favorable safety profile. These findings support NTRK gene fusion testing in patients with advanced salivary gland cancers. © 2022 The Author(s). |
| Keywords: | adult; clinical article; aged; overall survival; constipation; fatigue; case report; cisplatin; fluorouracil; drug efficacy; drug safety; paclitaxel; nuclear magnetic resonance imaging; follow up; adenocarcinoma; carboplatin; progression free survival; computer assisted tomography; myalgia; continuous infusion; histology; docetaxel; dizziness; drug dose escalation; dyspnea; alanine aminotransferase; aspartate aminotransferase; fluorescence in situ hybridization; gene fusion; salivary gland cancer; disease exacerbation; overall response rate; parotidectomy; high throughput sequencing; trk; mucoepidermoid tumor; human; male; female; article; salivary gland tumors; entrectinib; positron emission tomography-computed tomography; larotrectinib; ntrk |
| Journal Title: | The Oncologist |
| Volume: | 29 |
| Issue: | 6 |
| ISSN: | 1083-7159 |
| Publisher: | Oxford University Press |
| Date Published: | 2024-06-01 |
| Start Page: | e779 |
| End Page: | e788 |
| Language: | English |
| DOI: | 10.1093/oncolo/oyac080 |
| PUBMED: | 35536733 |
| PROVIDER: | scopus |
| PMCID: | PMC11144979 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledge in the PDF -- Source: Scopus |
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