Customize
Quick Links
Specialties

Accreditation/Credit Designation

Physicians' Education Resource®, LLC is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.

Physicians' Education Resource®, LLC designates this enduring material for a maximum of 2.0 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Acknowledgement of Commercial Support

This activity is supported by an educational grant from Merck Sharp & Dohme Corp.

New Frontiers in Immuno-Oncology for Microsatellite Instability-High Cancers

Release Date: August 29, 2017
Expiration Date: August 29, 2018
Media: Internet - based

 

Activity Overview

Community Practice Connections™: New Frontiers in Immuno-Oncology for Microsatellite-Instability-High Cancers is a continuing medical education (CME)-certified activity based on a symposium of the same name held in Chicago, Illinois, on June 5, 2017.

The significance of deficiencies in mismatch repair (MMR) pathways and microsatellite instability (MSI) toward the delivery of precision cancer care is evolving. MMR deficiencies and MSI are important components in the pathogenesis of certain solid tumors that carry both prognostic and predictive value. Results from clinical studies suggest that a variety of solid tumors that are deficient in MMR (dMMR)/have a MSI-high (MSI-H) phenotype have higher responses to immune checkpoint inhibition than do MMR-proficient tumors, and these findings have prompted further studies in this area. These investigations have already led to the FDA approval of the first tumor location-agnostic indication for a cancer therapy, with immunotherapy now being delivered based on genetic composition (ie, MSI-H) rather than tumor type.

This CME activity consists of a series of brief interviews with 3 expert faculty members exploring clinically relevant questions concerning the use of MSI status from the community physician perspective. We invite you to join these experts as they guide participants through this fascinating and potentially practice-transforming application of immunotherapy. Important topics addressed in this activity include:

  • dMMR/MSI testing considerations and recommendations
  • Potential role of MSI status as a predictive marker in solid tumors
  • Immunogenicity of dMMR/MSI-H tumors
  • Emerging clinical trial data regarding the use of immunotherapy for dMMR/MSI-H tumors

Acknowledgement of Commercial Support

This activity is supported by an educational grant from Merck Sharp & Dohme Corp.

CME Activity Table of Contents

  • Module 1. Overview of Mismatch Repair and Microsatellite Instability Testing
  • Module 2. Response to Immune Checkpoint Inhibition in Gastrointestinal Cancers and Impact of Microsatellite Instability Status
  • Module 3. Expanding Immunotherapy to Microsatellite Instability-High Nongastrointestinal Cancers: Emerging Clinical Data

Instructions for This Activity and Receiving Credit

  • You will need to login to participate in the activity.
  • Each presentation may contain an interactive question(s). You may move forward through the presentation; however, you may not go back to change answers or review videos/content until you finish the presentation.
  • At the end of the activity, “educational content/video files” will be available for your reference.
  • In order to receive a CME certificate, participants must complete the activity.
  • Complete the posttest and pass with a score of 70% or higher, complete the evaluation and then click on request for credit. Participants may immediately download a CME certificate upon completion of these steps.

Target Audience

This educational activity is directed toward medical oncologists who treat patients with solid tumors. Nurse practitioners, nurses, physician assistants, pharmacists, researchers, and other healthcare professionals interested in the treatment of solid tumors also are invited to participate.

Learning Objectives

At the conclusion of this activity, you should be better prepared to:

  • Explain the evolving roles for MMR deficiency and MSI testing in clinical oncology practice
  • Describe the relationship between MSI status and immunologic response, including evidence concerning the use of MSI as a predictive marker for response to checkpoint blockade
  • Evaluate current and emerging clinical trial results concerning the use of immunotherapeutic approaches in patients with MSI-H tumors
  • Delineate next steps in the field concerning the use of novel treatment strategies for the management of MSI-H cancers

Faculty, Staff, and Planners' Disclosures

Program Chair

Wells Messersmith, MD, FACP
Professor and Head, Division of Medical Oncology
Director, GI Medical Oncology Program
Co-Leader, Developmental Therapeutics Program
University of Colorado Cancer Center
University of Colorado School of Medicine
Denver, CO

Disclosure: Grant/Research Support: Roche/Genentech, Pfizer, Immunomedics, OncoMed, Alexo; Consultant: Gilead.

Faculty

Cathy Eng, MD, FACP
Director and Professor
Department of Gastrointestinal Medical Oncology
Associate Medical Director Colorectal Center
Division of Cancer Medicine
The University of Texas MD Anderson Cancer Center
Houston, TX

Disclosure: Grant/Research Support: Daiichi, Keryx; Consultant: Bayer, Sirtex; Speakers Bureau: Genentech, Taiho; Other: Honoraria ‒ Roche Genentech, Bayer.

Dung Le, MD
Medical Oncology
Sidney Kimmel Comprehensive Cancer Center
Johns Hopkins University School of Medicine
Bunting-Blaustein Cancer Research Building
Baltimore, MD

Disclosure: Grant/Research Support: Merck, BMS; Consultant: Merck.

Bradley J. Monk, MD, FACS, FACOG
Arizona Oncology (US Oncology Network)
Professor, Gynecologic Oncology: University of Arizona and Creighton University
Phoenix, AZ
 
 

Disclosure: Grant/Research Support: Amgen, Genentech, Lilly, Array, TESARO, Morphotek, Janssen/Johnson & Johnson; Consultant: Merck, TESARO, Gradalis, Advaxis. Amgen, Insys, Clovis, Mateon (formerly Oxigene), Roche/Genentech, AstraZeneca, Pfizer, PPD, Precision Oncology, Perthera, Biodesix, ImmunoGen, Cue; Speakers Bureau: Roche/Genentech, AstraZeneca, Janssen/Johnson & Johnson, Clovis, TESARO.

The staff of PER® have no relevant financial relationships with commercial interests to disclose.

Disclosure Policy and Resolution of Conflicts of Interest (COI)

As a sponsor accredited by the ACCME, it is the policy of PER® to ensure fair balance, independence, objectivity, and scientific rigor in all of its CME activities. In compliance with ACCME guidelines, PER® requires everyone who is in a position to control the content of a CME activity to disclose all relevant financial relationships with commercial interests. The ACCME defines “relevant financial relationships” as financial relationships in any amount occurring within the past 12 months that creates a COI.

Additionally, PER® is required by ACCME to resolve all COI. PER® has identified and resolved all COI prior to the start of this activity by using a multistep process.




PER Pulse™ Recap (1 of 3)

The live continuing medical education activity New Frontiers in Immuno-Oncology for Microsatellite-Instability-High Cancers, held adjunct to an annual oncology meeting in Chicago, Illinois, featured the following experts discussing the latest clinical research on microsatellite-instability-high (MSI-H) tumors: Wells Messersmith, MD, FACP; Cathy Eng, MD, FACP; Dung Le, MD; and Bradley Monk, MD, FACS, FACOG. This program featured engaging lectures on research supporting immune checkpoint inhibitors for the treatment of MSI-H cancers, regardless of tumor type. This first of 3 PER Pulse™ Recaps reviews the rationale for assessing mismatch repair (MMR) and the considerations important for MSI testing.

Below are some take-home messages from Dr Eng’s lecture:

  • MSI is a phenotype (showing variations in genomic repeat sequences called microsatellites) that arises from tumors that are deficient in MMR due to germline or somatic mutations
  • MMR testing is performed using immunohistochemistry (IHC) to measure the presence of 4 different MMR proteins: MLH1, MSH2, MSH6, and PMS2
  • MSI testing is performed using polymerase chain reaction (PCR) to compare microsatellite length in tumor and germline tissue
  • MSI testing can also been accomplished using next-generation sequencing
  • Both MMR and MSI assays measure the same biological effect
  • MSI-H is the hallmark genetic aberration of Lynch syndrome, an autosomal dominant genetic condition associated with an increased lifetime risk of colon, endometrial, and other cancers
  • Tumors can also acquire the MSI-H phenotype via somatic mutations (sporadic cancer)
  • The presence or absence of BRAF mutation can provide information on the risk of Lynch syndrome, as the presence of a BRAF mutation strongly suggests sporadic pathogenesis
  • All patients with colorectal cancer should be tested for MMR/MSI

For additional commentary about this topic and the New Frontiers in Immuno-Oncology for Microsatellite-Instability-High Cancers symposium, please visit www.gotoper.com.




PER Pulse™ Recap (2 of 3)

The live continuing medical education activity “New Frontiers in Immuno-Oncology for Microsatellite-Instability-High Cancers,” held adjunct to an annual oncology meeting in Chicago, Illinois, featured the following experts discussing the latest clinical research on microsatellite-instability-high (MSI-H) tumors: Wells Messersmith, MD, FACP; Cathy Eng, MD, FACP; Dung Le, MD; and Bradley Monk, MD, FACS, FACOG. This program featured engaging lectures on research supporting immune checkpoint inhibitors for the treatment of MSI-H cancers, regardless of tumor type. This second of 3 PER Pulse™ Recaps discusses the data available on the use of immune checkpoint inhibitors in colorectal and other gastrointestinal (GI) cancers.

Below are some take-home messages from Dr Le’s lecture:

  • Immune checkpoint inhibitors are active in nearly all GI malignancies
  • The histologic features of MSI-H colorectal cancer (CRC) include mucinous histology, signet-ring cell differentiation, intra- and peritumoral lymphocytes, medullary carcinoma, and poor differentiation
  • MSI-H tumors have higher levels of tumor mutation burden (TMB), and TMB is positively correlated with clinical benefit from immune checkpoint inhibitors
  • In KEYNOTE-016, patients with CRC tumors were divided into cohorts based on mismatch repair (MMR) status
    • Responses were restricted to the MMR-deficient cohort (objective response rate [ORR], 57% vs 0%)
    • Median progression-free survival and overall survival were not reached in the MMR-deficient cohort, whereas they were 2.3 months and 5.98 months, respectively, in the MMR-proficient cohort
  • In a study of 74 patients with previously treated MMR-deficient/MSI-H CRC, patients received nivolumab alone or in combination with ipilimumab
    • In the nivolumab-alone arm, ORR was 32.1% and stable disease (SD) was 39.6%
    • In the combination-therapy arm, ORR was 33.3% and SD was 51.9%

For additional commentary about this topic and the New Frontiers in Immuno-Oncology for Microsatellite-Instability-High Cancers symposium, please visit www.gotoper.com.




PER Pulse™ Recap (3 of 3)

The live continuing medical education activity New Frontiers in Immuno-Oncology for Microsatellite-Instability-High Cancers, held adjunct to an annual oncology meeting in Chicago, Illinois, featured the following experts discussing the latest clinical research on microsatellite-instability-high (MSI-H) tumors: Wells Messersmith, MD, FACP; Cathy Eng, MD, FACP; Dung Le, MD; and Bradley Monk, MD, FACS, FACOG. This program featured engaging lectures on research supporting immune checkpoint inhibitors for the treatment of MSI-H cancers, regardless of tumor type. This third of 3 PER Pulse™ Recaps describes the clinical data available on the use of immune checkpoint inhibition for nongastrointestinal (GI) cancers.

Below are some take-home messages from Dr Monk’s lecture:

  • The MSI-H phenotype is present in a subset of a wide array of tumor types
    • Tumors with MSI-H subsets of at least 10% incidence include colorectal cancer (CRC), gastric cancer, hepatocellular carcinoma, thyroid cancer, ampullary cancer, endometrial cancer, melanoma, and other skin cancers
    • Tumors with MSI-H subsets with an incidence of 2% to 10% include ovarian, cervical, and head and neck cancers, esophageal adenocarcinoma, soft tissue sarcoma, renal cell carcinoma, and Ewing sarcoma
  • Approximately 28% to 35% of endometrial cancers are mismatch repair (MMR) deficient
    • For endometrial cancers, the National Comprehensive Cancer Network recommends universal MMR testing at the time of hysterectomy
  • In May 2017, the FDA made the groundbreaking announcement that pembrolizumab had earned the first location-agnostic indication for a cancer therapy, approving it for the treatment of MSI-H solid tumors that have progressed following prior treatment and for which there are no satisfactory alternative treatment options
  • This approval was based on data from 149 patients with 15 different types of MSI-H advanced cancers from 5 different clinical trials
    • The objective response rate (ORR) to pembrolizumab in the overall MSI-H population was 39.6%, with 78% of responding patients having a duration of response of at least 6 months
    • For all tumor types having more than 2 patients, the ORR ranged from 27% (biliary cancer) to 83% (pancreatic cancer)
    • For the 2 most common tumor types in the analysis—CRC and endometrial cancer—the ORR was 36% for each
    • At 1 year, the progression-free survival rate of the entire MSI-H population was 57% and the overall survival rate was 81%

For additional commentary about this topic and the New Frontiers in Immuno-Oncology for Microsatellite-Instability-High Cancers symposium, please visit www.gotoper.com.








Become a Member

Forgot Password?
Calendar of Events
SUNMONTUESWEDTHURSFRISAT
1234567
891011121314
15161718192021
22232425262728
293031
Filter By