Overview

Despite significant advancements over the past decade, significant unmet needs persist for patients with NTRK-positive locally advanced or metastatic solid tumors.  In addition, there is ongoing debate about the importance of testing for genomic alterations in rare cancers, or those that rarely occur in common cancers. However, evolving molecular testing procedures and emerging therapeutic options targeting NTRK fusions offer new pathways for the detection and treatment of these cancers. To help clinicians enhance their diagnostic-therapeutic paradigms for rare genomic alterations, this interactive practice guide interweaves education and practical guidance for easy integration of the latest testing and treatment strategies within daily clinical processes and workflows.

This activity is created for medical oncologists, pathologists, nurse practitioners, physician assistants and APNs who care for patients with NTRK fusion-positive cancers.

Neurotrophic tropomyosin-receptor kinases (NTRKs) play a pivotal role in neural development and NTRK gene fusions (ie, NTRK1, NTRK2, and NTRK3) have been identified as oncogenic drivers of various adult and pediatric tumor types. Although these mutations are infrequent (<1%) in a range of common tumor types including colorectal cancer (CRC), thyroid, soft tissue sarcoma, melanoma, and non-small cell lung cancer (NSCLC), NTRK fusions are observed at high frequencies (up to or greater than 90%) in rare cancer types including secretory breast carcinoma, mammary analogue secretory carcinoma, and infantile fibrosarcoma. However, due to the rarity of these alterations, determining the optimal testing strategy based on available resources remains a practical challenge. The challenges in detecting NTRK fusions are of particular importance when considering the development of targeted tropomyosin receptor kinase (TRK) inhibitors, including first-generation therapies larotrectinib and entrectinib that have demonstrated efficacy and acceptable safety profiles in locally advanced, and metastatic cancers that express NTRK gene fusions. Despite high responses to these first-generation agents, primary and acquired resistance have often been observed. Consequently, next-generation TRK inhibitors such as selitrectinib and repotrectinib have been designed to overcome acquired resistance to first-generation TRK inhibitors. As a result of these advancements and the changing treatment landscape, staying current with emerging data and their impact on treatment paradigms can be challenging. It is critical for treating physicians, molecular pathologists, and other healthcare professionals to remain current on the molecular testing and treatment landscapes for NTRK fusion-positive cancers to improve and personalize patient care through an examination of current practices to develop strategies to optimize processes and workflows in routine clinical practice.

Upon completion of this activity, learners will be able to:
• Review optimal testing strategies to detect NTRK fusions in patients with cancer
• Assess efficacy and safety data of current and emerging TRK inhibitors for patients with NTRK fusion-positive advanced solid tumors
• Establish operational frameworks to improve precision medicine practices in patients with NTRK fusion-positive cancers

Provided by The University of Chicago Pritzker School of Medicine and the Academy for Continued Healthcare Learning (ACHL).

Supported by an educational grant from Bristol Myers Squibb.