Establishing Frameworks for Precision Medicine in NTRK Fusion-Positive Advanced Solid Tumors

Release/ Expiration Date

August 15, 2024 - August 15, 2025

Activity Description

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.

Activity Purpose

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.

Target Audience

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

Learning Objectives

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

Accreditation Statement

The University of Chicago Pritzker School of Medicine is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.

Credit Designation

The University of Chicago Pritzker School of Medicine designates this enduring material for a maximum of 1.0 AMA PRA Category 1 Credit™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Physician assistants, nurse practitioners, and nurses may participate in this educational activity and earn a certificate of completion as AAPA, AANP, and ANCC accept AMA PRA Category 1 Credits™ through their reciprocity agreements.

MIPS Improvement Activity

Completion of this activity, including the pretest, posttest, and follow-up assessments, qualifies as a medium weight MIPS improvement activity under MACRA and can be claimed as completion of IA_PSPA 28 of an Accredited Safety or Quality Improvement Program in the Quality Payment Program. Clinicians should submit their improvement activities by attestation via the CMS Quality Payment Program website. You will receive additional information after completing the activity and receiving your certificate via email.

Method of Participation

This activity will take approximately 60 minutes to complete. To receive credit, learners are required to complete the pretest, view the online activity, and complete the posttest and evaluation. To receive credit, 66% must be achieved on the posttest. A certificate will be immediately available. There is no fee to participate in the activity or for the generation of the certificate.

For questions, contact McKenna Reinhard at mreinhard@achlcme.org.

Disclaimer

The content for this activity was developed independently of any ineligible company. All materials are included with permission. The opinions expressed are those of the faculty and are not to be construed as those of the publisher or grantor(s).

This educational activity was planned and produced in accordance with the ACCME Standards for Integrity and Independence in Accredited Continuing Education. Recommendations involving clinical medicine in a continuing medical education (CME/CE) activity must be based on evidence that is accepted within the profession of medicine as adequate justification for their indications and contraindications in the care of patients. All scientific research referred to, reported, or used in CME/CE in support or justification of a patient care recommendation must conform to the generally accepted standards of experimental design, data collection, and analysis.

This CME/CE activity might describe the off-label, investigational, or experimental use of medications and/or devices that may exceed their FDA-approved labeling. Physicians should consult the current manufacturers’ prescribing information for these products. ACHL and The University of Chicago requires the speaker to disclose that a product is not labeled for the use under discussion.

Discussion of scientific information on unapproved uses (SIUU), off-label, investigational, or experimental drug/device use: selitrectinib

Faculty

Alexander Drilon, MD
Chief, Early Drug Development
Assistant Attending, Thoracic Oncology
Memorial Sloan Kettering Cancer Center
New York, NY

Jeremy Segal, MD, PhD
Professor, Pathology
University of Chicago
Director, Molecular and Cytogenic Pathology
University of Chicago Medicine
Chicago, IL

Faculty Disclosures

As a provider accredited by the ACCME, The University of Chicago Pritzker School of Medicine asks everyone in a position to control the content of an education activity to disclose all financial relationships with any ineligible companies. This includes any entity whose primary business is producing, marketing, selling, re-selling, or distributing healthcare products used by or on patients. Financial relationships are relevant if a financial relationship, in any amount, exists between the person in control of content and an ineligible company during the past 24 months, and the content of the education is related to the products of an ineligible company with whom the person has a financial relationship. Mechanisms are in place to identify and mitigate any relevant financial relationships prior to the start of the activity.

Additionally, The University of Chicago Pritzker School of Medicine requires Authors to identify investigational products or off-label uses of products regulated by the US Food and Drug Administration at first mention and where appropriate in the content.

The following financial relationships have been provided:
Alexander Drilon, MD (Chair)
Honoraria recipient: 14ner/Elevation Oncology, Amgen, Abbvie, ArcherDX, AstraZeneca, Beigene, BergenBio, Blueprint Medicines, Bristol Myers Squibb, Boehringer Ingelheim, Chugai Pharmaceutical, EcoR1, EMD Serono, Entos, Exelixis, Helsinn, Hengrui Therapeutics, Ingyta/Genentech/Roche, Janssen, Lozo/Bayer/Lilly, Merus, Monopteros, monteRosa, Novartis, Nuvalent, Pfizer, Prelude, Regeneron, Repare RX, Springer Healthcare, Takeda/Ariad/Millenium, Treeline Bio, TP Therapeutics, Tyra Biosciences, Verastem
Advisory Boards: Abbvie, Amgen, AnHeart Therapeutics, Bayer, EcoR1 Capital, LLC, Helsinn, Loxo/Lill, MonteRosa, Novartis
Consulting:14ner/Elevation Oncology, Boundless Bio, Entos, Innocare, MonteRosa, Nuvalent, Prelude, Treeline bio, Zymeworks
Royalties: Wolters Kluwer
Food/beverage: Boehringer Ingelheim, Merck, Puma
CME Honoraria: Answers in CME, Applied Pharmaceutical Science, Inc, AXIS, Clinical Care Options, Doc Congress, EPG Health, Harborside Nexus, I3 Health, Imedex, Liberum, Medendi, Medscape, Med Learning, MedTalks, MJH Life Sciences, MORE Health, Ology, OncLive, Paradigm, Peerview Institute, PeerVoice, Physicians Education, Projects in Knowledge, Resources, Remedica Ltd, Research to Practice, RV More, Targeted Oncology, TouchIME, WebMD

Jeremy Segal, MD, PhD (Chair)
Advisory Board: Abbvie (relationship has ended), Astrazeneca (relationship has ended), OrisDx

Staff and Reviewer Disclosures

The University of Chicago Pritzker School of Medicine, ACHL staff members and others involved with the planning, development, and review of the content for this activity have no relevant affiliations or financial relationships to disclose.

Providership

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

Commercial Support

Supported by an educational grant from Bristol Myers Squibb.

Copyright Statement

© 2024 Academy for Continued Healthcare Learning
Academy for Continued Healthcare Learning
308 S Jefferson St, Suite 312
Chicago, IL 60661-5605
Ph (877) 444-8435
www.ACHLcme.org