What the Heck is NTRK?

What the Heck is NTRK? Posted By:
...

Neurotrophic receptor tyrosine kinase (NTRK) is a gene, and when it fuses to an unrelated gene in some cancers it can become a driver for cancer growth. Two drugs have recently been approved to manage NTRK-positive cancers, so it is worthwhile to discuss how we find this gene fusion and how it can be managed.

NTRK gene fusion is rare. It is frequently found in salivary tumors, though these tumors usually do not require systemic treatment and can be locally managed. It is also found in about 1% of non-small cell lung cancer (NSCLC), sarcomas, GI cancers, and glioblastomas. It is a bit more common in thyroid cancers—up to 10%—though these are also managed with local therapies.

Detection techniques for NTRK gene fusion can be tricky to understand. NTRK gene fusion should be detected on an RNA fusion transcript panel. This is not to be confused with a DNA sequencing panel, such as Next Generation Sequencing, which is the most common platform currently used to detect molecular mutations. A DNA sequencing panel may show NTRK positivity, but NTRK found on DNA sequencing panels has not shown the sensitivity to the NTRK-targeted drugs that the RNA panel detects. So the testing company or hospital should run a separate RNA fusion panel to detect NTRK that is associated with sensitivity to these drugs.

Larotrectinib was the first drug approved, in December 2018, for any solid tumor that tests positive for NTRK gene fusion. The approval was based on robust and durable response rates after failure of chemotherapy. The majority of patients in the trial by Drilon and colleagues had salivary gland tumors or sarcomas, and larotrectinib was given as a pill taken twice a day. The most common adverse effects were increases in liver transaminases, fatigue, nausea/vomiting, and dizziness.

Entrectinib was the second drug approved, in August 2019, for NTRK-positive solid tumors and ROS1-positive NSCLC. For the NTRK-positive indication, this drug is used for adult and pediatric tumors. In pediatric patients, there was a 100% response rate in all 11 patients, for both solid and central nervous system tumors, while there were no responses in pediatric patients who lacked the NTRK gene fusion. In 53 patients worldwide with ROS1-positive NSCLC treated with entrectinib, there was a 77% response rate with a median duration of response of 2 years. The adverse effects were similar to those of larotrectinib.

NTRK is a novel target, now with two quick drug approvals. While NTRK gene fusion is rare, when it is found, NTRK-targeted drugs demonstrate remarkable response rates and duration of response with minimal toxicities.

References
  • Doebele RC, Ahn MJ, Siena S, et al. Efficacy and safety of entrectinib in locally advanced or metastatic ROS1-positive non-small cell lung cancer. Presented at: 2018 World Conference on Lung Cancer; September 24, 2018. Abstract 13903.
  • Drilon A, Laetsch TW, Kummar S, et al. Efficacy of larotrectinib in TRK fusion-positive cancers in adults and children. N Engl J Med. 2018;378:731-739.
  • Robinson GW, Gajjar AJ, Gauvain KM, et al. Phase 1/1B trial to assess the activity of entrectinib in children and adolescents with recurrent or refractory solid tumors including central nervous system (CNS) tumors. J Clin Oncol. 2019;37(suppl). Abstract 10009.

Share

Filed under: Oncology/Hematology

Sign up to receive posts from The Exchange

Related
My Experience Managing Key Adverse Events With Oral Targeted Therapy for High-Risk Early Breast Cancer

My Experience Managing Key Adverse Events With Ora ...

Recent years have seen the approval of oral targeted therapy options for the treatment of high-risk ...

Filed under: Oncology/Hematology, NPs & PAs


Continue Reading
Maximizing Benefit With the Expanding Options for Gastric Cancer: Expert Answers to Frequently Asked Questions

Maximizing Benefit With the Expanding Options for ...

In this post, James M. Cleary, MD, PhD, answers key questions from attendees of a webinar developed ...

Filed under: Oncology/Hematology, NPs & PAs


Continue Reading
Inpatient and Outpatient Management of Immune-Related Adverse Events

Inpatient and Outpatient Management of Immune-Rela ...

Immune checkpoint inhibitors (ICIs) carry the unique risk of a highly unpredictable class of toxicit ...

Filed under: Oncology/Hematology, NPs & PAs


Continue Reading
Counseling Patients and Caregivers on Immune-Related Adverse Events

Counseling Patients and Caregivers on Immune-Relat ...

In this commentary, Alexa Basilio, PharmD, BCOP, and Jordan McPherson, PharmD, MS, BCOP, discuss imp ...

Filed under: Oncology/Hematology, NPs & PAs


Continue Reading
Practical Insights for NPs and PAs: Biomarker Testing in NSCLC

Practical Insights for NPs and PAs: Biomarker Test ...

In 2023, approximately 50% of patients with advanced nonsquamous non-small-cell lung cancer (NSCLC) ...

Filed under: Oncology/Hematology, NPs & PAs


Continue Reading
Current Therapeutic Strategies for Advanced Melanoma

Current Therapeutic Strategies for Advanced Melano ...

Are you up to date on current recommendations for the care of your patients with advanced melanoma? ...

Filed under: Oncology/Hematology, NPs & PAs


Continue Reading