13 Feb Larotrectinib – VITRAKVI® – in Patients with TRK Fusion Gastrointestinal Cancer

MedicalResearch.com Interview with:

Dr. Hong

Dr. David S. Hong MD
Deputy Chair
Department of Investigational Cancer Therapeutics
Division of Cancer MedicineThe University of Texas MD Anderson Cancer Center
Houston, TX 

MedicalResearch.com: What is the background for this study? What are the main findings?

• A rare genomic alteration called a neurotrophic receptor tyrosine kinase (NTRK) gene fusion is a primary oncogenic driver that causes TRK fusion cancer, which has been found in a variety of common tumor types, including GI cancers such as colon, cholangiocarcinoma, pancreatic, and appendiceal cancers. In patients with gastrointestinal (GI) cancer, including pancreatic cancer and colorectal cancer, NTRK gene fusions are estimated to have a frequency of ~0.3%.
• Larotrectinib is an oral and highly selective TRK inhibitor used for the treatment of adult and pediatric patients with solid tumors that have an NTRK gene fusion. Under the brand name Vitrakvi^®, it is the first and only approved TRK inhibitor exclusively designed to treat tumors with an NTRK gene fusion with approval in the US in 2018 and other worldwide markets in 2019.
• At ASCO GI 2020, we presented results of a new analysis of the efficacy and safety of larotrectinib specifically in patients with TRK fusion with gastrointestinal cancers, which is an often underdiagnosed patient group. The subset included 14 adult patients with GI tumor types with NTRK gene fusions, including colon, cholangiocarcinoma, pancreas, appendix and hepatic; of the eight patients with colon cancer, seven were microsite instability (MSI)-high.
• In this subset of patients, the overall response rate (ORR) was 43%. Additionally, median overall survival was 33.4 months at 19 months of follow-up (range 2.8–36.5), median progression-free free survival (PFS) was 5.3 months (range 2.2-9.0) and median time to response was 1.8 months (range 1.7-2.1). In colon cancer patients, the ORR was 50% and the median PFS ranged from 1.5+ to 16.7+ months. 

MedicalResearch.com: What should readers take away from your report?

Response: This analysis and the growing pool of data in different patient subsets further confirm the consistent efficacy and safety of larotrectinib in patients with TRK fusion cancer regardless of tumor type and age. The subanalysis emphasizes the role of NTRK gene fusions in gastrointestinal tumors, paving the way to help identify often undiagnosed patients; and the strong results with larotrectinib we presented at ASCO GI support a potential new treatment option for the GI community, helping to fill gaps in treatment and address unmet patient needs.

MedicalResearch.com: What recommendations do you have for future research as a result of this work?

• Of the eight patients with colon cancer in this study, seven were microsite instability (MSI)-high, which is consistent with ongoing research that indicates NTRK gene fusions occur more frequently in the MSI-high subset of colorectal patients. This data and the strong responses we continue to see with larotrectinib encourages broader adoption and further research of genomic cancer testing to identify gene mutations, especially in patients with MSI-high colon cancer.
• We now know that cancer is a disease of the genome and the only method to uncover NTRK gene fusions through genomic cancer testing. Future research focusing on the benefits of introducing genomic testing earlier in a cancer diagnosis approach would help guide treatment approach and implement the shift towards precision medicine in oncology in day-today practice. 

MedicalResearch.com: Is there anything else you would like to add? Any disclosures?

• Research/Grant Funding: AbbVie, Adaptimmune, Aldi-Norte, Amgen, Astra-Zeneca, Bayer, BMS, Daiichi-Sankyo, Eisai, Fate Therapeutics, Genentech, Genmab, GSK, Ignyta, Infinity, Kite, Kyowa, Lilly, LOXO, Merck, MedImmune, Mirati, miRNA, Molecular Templates, Mologen, NCI-CTEP, Novartis, Pfizer, Seattle Genetics, Takeda, Turning Point Therapeutics
• Travel, Accommodations, Expenses: Bayer, LOXO, miRNA, Genmab, AACR, ASCO, SITC
• Consulting or Advisory Role: Alpha Insights, Amgen, Axiom, Adaptimmune, Baxter, Bayer, eCancer, Genentech, GLG, Group H, Guidepoint, Infinity, Medscape, Numab, Oncology Education Project Association, Pfizer, Prime Oncology, Takeda, Trieza Therapeutics, WebMD
• Other ownership interests: Molecular Match (Advisor), OncoResponse (Founder), Presagia Inc (Advisor)

Citation:

ASCO GI Abstract January2020

Efficacy and safety of larotrectinib in patients with TRK fusion gastrointestinal cancer.

Jordan Berlin, David S. Hong, John F. Deeken, Valentina Boni, Do-Youn Oh, Jyoti D. Patel, Shivani Nanda, Nicoletta Brega, Barrett H. Childs, David Michael Hyman, and Alexander E. Drilon

Journal of Clinical Oncology 2020 38:4_suppl, 824-824

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Last Updated on February 13, 2020 by Marie Benz MD FAAD