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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 live activity for a maximum of 1.5 AMA PRA Category 1 Credits™. Physicians should claim only the credits commensurate with the extent of their participation in the activity.

Acknowledgment of Commercial Support

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

Enduring CME activity from the September 4, 2018, Live Webcast: Meeting Unmet Clinical Needs in Cervical Cancer: Paving a New Course in Advanced Disease Settings With Immune-Based Strategies


Release Date: September 28, 2018
Expiration Date: September 28, 2019
Media: Internet - based

Activity Overview

This enduring CME activity is an archive of the live broadcast from September 4, 2018, titled Meeting Unmet Clinical Needs in Cervical Cancer: Paving a New Course in Advanced Disease Settings With Immune-Based Strategies. This activity features a panel of gynecologic oncology experts providing you with a multifaceted overview of the application of immune-based strategies in the care of patients with advanced cervical cancer. During the webcast, the faculty discuss many aspects of the use of immunotherapies for the management of this disease, presenting divergent views of complex and controversial topics, thereby providing you with a more comprehensive understanding of the issues and informing your clinical decision-making.

This enduring CME activity offers education to augment your clinical competence in several areas, including:

  • Use of biomarkers to select patients with advanced cervical cancer for immune-based approaches
  • Integration of checkpoint inhibitors into the management of advanced cervical cancer
  • Mitigation of immune-related adverse events associated with immunotherapeutic approaches
  • Sequencing of multiple lines of therapy for patients with advanced cervical cancer

The format of this archived live broadcast is an in-studio panel discussion where the faculty briefly didactically present immunotherapy rationale and clinical trial data, after which they discuss and debate the practical application of this approach for patients with advanced cervical cancer. The panel also answers several questions submitted by viewers. The webcast has been divided into modules for your ease of access, and it brings conference-caliber education to the convenience of your screen!

Benefits of Participating

  • Insights into the use of biomarkers to select patients with advanced cervical cancer for immune-based approaches
  • Improved competence for integrating checkpoint inhibitors into the management of advanced cervical cancer
  • Strategies to mitigate immune-related adverse events associated with immunotherapeutic approaches
  • Opportunity to have your questions answered live by the faculty to gain expert insight into this difficult-to-treat tumor type

Acknowledgement of Commercial Support

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 live activity for a maximum of 1.5 AMA PRA Category 1 Credits™. Physicians should claim only the credits commensurate with the extent of their participation in the activity.

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 and gynecologists who treat patients with cervical tumors. Nurse practitioners, nurses, physician assistants, pharmacists, researchers, and other healthcare professionals interested in the treatment of cervical tumors may also participate.

Learning Objectives

Upon completion of this activity, you should be better prepared to:

  • Describe the rationale for the development of immunotherapies in the setting of cervical cancer
  • Summarize outcomes from immunotherapy clinical trials conducted in patients with advanced cervical cancer
  • Use cases to illustrate where and how immunotherapy agents fit within the care of patients with advanced cervical cancer
  • Outline strategies to alleviate immune-related adverse events in patients with cervical cancer

Faculty, Staff, and Planners' Disclosures

Chair

Bradley J. Monk, MD, FACS, FACOG
Professor, Division of Gynecologic Oncology
Arizona Oncology (US Oncology Network)
University of Arizona College of Medicine
Phoenix Creighton University School of Medicine at St. Joseph’s Hospital
Phoenix, AZ

Disclosure: Consultant: AbbVie, Advaxis, Amgen, Biodesix, Genmab, Gradalis, ImmunoGen, Immunomedics, Incyte, Mateon (formally Oxigene), Merck, Myriad, Perthera, Pfizer, Precision Oncology, Puma, Samumed, Takeda, VBL; Speaker/Consultant: AstraZeneca, Clovis, Janssen/Johnson & Johnson, Roche/Genentech, TESARO, Inc.

Faculty

Linda R. Duska, MD, MPH, FACOG
Professor of Obstetrics and Gynecology
University of Virginia
Charlottesville, VA
 
 

Disclosure: Grant/Research Support: Merck, Novartis (research funding to department); Consultant/Advisory Board: Merck, Genentech

Shannon N. Westin, MD, MPH, FACOG
Associate Professor
Department of Gynecologic Oncology and Reproductive Medicine
Director, Early Drug Development
The University of Texas MD Anderson Cancer Center
Houston, TX

Disclosure: Grant/Research Support: AstraZeneca, Genentech, Clovis, Tesaro, Bayer, Novartis, Cotinga Pharmaceuticals; Consultant: AstraZeneca, Roche/Genentech, Clovis, Tesaro, Merck, Ovation, Medivation, OncLive, Medscape

Planner

Krishnansu S. Tewari, MD, FACOG, FACS, FRSM
Professor-in-Residence & Interim Division Director
Department of Obstetrics & Gynecology
The University of California, Irvine
Orange, CA

Disclosure: Grant/Research Support: AstraZeneca, AbbVie, Morphotek, Genentech, Regeneron, Merck; Consultant: Regeneron, Spectrum, Genentech, Que, Agenus, Tesaro, Clovis, AstraZeneca; Speaker's Bureau: Clovis, Tesaro

The staff of Physicians’ Education Resource®, LLC 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™ Recaps

PER® Pulse Recap
1 of 3
 
Rationale for the Use of Immunotherapy for Cervical Cancer
 
The online CME activity, Meeting Unmet Clinical Needs in Cervical Cancer: Paving a New Course in Advanced Disease Settings With Immune-Based Strategies, provides oncologists and other practitioners with an engaging discussion from several leading cervical cancer experts, including Bradley J. Monk, MD, FACS, FACOG, Professor and Director of the Division of Gynecologic Oncology at Creighton University School of Medicine, St. Joseph’s Hospital and Medical Center, Phoenix, AZ; Linda R. Duska, MD, MPH, FACOG, Professor of Obstetrics and Gynecology and Associate Dean for Clinical Research at the University of Virginia School of Medicine, Charlottesville; and Shannon N. Westin, MD, MPH, FACOG, Associate Professor in the Department of Gynecologic Oncology and Reproductive Medicine, Division of Surgery, and Director of Early Drug Development at The University of Texas MD Anderson Cancer Center, Houston.

This first of 3 PER Pulse Recaps from the program focuses on the rationale for the use of immunotherapy in cervical cancer. Dr. Westin summarized information supporting a role for an immunologic approach to the management of cervical cancer:

  • With other abnormalities associated with human papillomavirus (HPV) infections, such as genital warts, several factors indicate that cell-mediated immunity is involved in their regression. For instance, in regressing genital warts, a large infiltrate of macrophages and CD4+ and CD8+ T cells are present, as are proinflammatory cytokines (ie, interleukin-12, tumor necrosis factor-alpha, and interferon-gamma [IFN-γ]). There is also an upregulation of adhesion molecules, which are required for lymphocyte trafficking.
  • Immunosuppressed HIV+ individuals have an increased incidence and progression of HPV infections.
  • In cervical cancer, the IFN-γ signaling pathway shows significant genetic mutations.
  • Certain cervical cancers—those with a squamous cell histology—have been found to have high somatic copy number alterations. Moreover, regardless of histology, cervical cancers have genetic amplifications that correlate significantly with granzyme A and perforin 18, 2 key immune cytolytic effector genes.

Dr. Westin also discussed the different immune checkpoint (ICP) pathways that may be targeted to attack cervical cancers. She pointed out that, in addition to the most well-known ICP pathway of PD-1, there are other pathways that may also have actionable targets. These include the CTLA-4, LAG3, and TIM3 pathways.

 
2 of 3
 
Current Data With Immunotherapy for Cervical Cancer
 
The online CME activity, Meeting Unmet Clinical Needs in Cervical Cancer: Paving a New Course in Advanced Disease Settings With Immune-Based Strategies, provides oncologists and other practitioners with an engaging discussion from several leading cervical cancer experts, including Bradley J. Monk, MD, FACOG, FACS, Professor and Director of the Division of Gynecologic Oncology at Creighton University School of Medicine, St. Joseph’s Hospital and Medical Center, Phoenix, AZ; Linda R. Duska, MD, MPH, FACOG, Professor of Obstetrics and Gynecology and Associate Dean for Clinical Research at the University of Virginia School of Medicine, Charlottesville; and Shannon N. Westin, MD, MPH, FACOG, Associate Professor in the Department of Gynecologic Oncology and Reproductive Medicine, Division of Surgery, and Director of Early Drug Development at The University of Texas MD Anderson Cancer Center, Houston.
 
This second of 3 PER Pulse Recaps from the program focuses on current data with immunotherapy for cervical cancer. Dr. Monk discussed the data currently available regarding the use of immunotherapy to treat cervical cancer:
 

  • He began by mentioning the presentation of results from 2 immunotherapy trials—CheckMate 358 and KEYNOTE-158—at the 2017 Annual Meeting of the American Society of Clinical Oncology.
  • In CheckMate 358, 24 patients with gynecologic cancers (19 of whom had cervical cancer) were treated with nivolumab, and 20.8% responded to therapy.
  • In the first presentation of data in cervical cancer from KEYNOTE-158, 47 patients with cervical cancer had a 12% response rate to pembrolizumab. In Cohort E of this same study, 98 patients were enrolled; 79% of them had tumors that were PD-L1–positive, and 65% had received at least 2 prior lines of therapy in the recurrent or metastatic setting. The response rate in this cohort (with 77 evaluable patients) was 14.3%, and this provided the basis for the accelerated approval by the US Food and Drug Administration (FDA) of pembrolizumab in patients with recurrent or metastatic PD-L1–positive cervical cancer that progressed on or after chemotherapy.

Following Dr. Monk’s presentation, faculty members had an informative discussion about the justification of the FDA approval of pembrolizumab on the basis of a 14% response rate, citing the remarkably durable responses and favorable safety profile of pembrolizumab, as well as the limited treatment options for this patient population. They also reviewed the status of biomarkers in this setting, pointing out the need for an improved biomarker. Ideally, biomarkers identify which patients are likely to respond to therapy, but in the case of pembrolizumab, PD-L1 expression simply identifies those patients who are NOT likely to respond to therapy, without being able to predict which patients WILL respond to checkpoint inhibition.


3 of 3
 
Managing Toxicities in Patients Receiving Immunotherapy for Cervical Cancer
 
The online CME activity, Meeting Unmet Clinical Needs in Cervical Cancer: Paving a New Course in Advanced Disease Settings With Immune-Based Strategies, provides oncologists and other practitioners with an engaging discussion from several leading cervical cancer experts, including Bradley J. Monk, MD, FACOG, FACS, Professor and Director of the Division of Gynecologic Oncology at Creighton University School of Medicine, St. Joseph’s Hospital and Medical Center, Phoenix, AZ; Linda R. Duska, MD, MPH, FACOG, Professor of Obstetrics and Gynecology and Associate Dean for Clinical Research at the University of Virginia School of Medicine, Charlottesville; and Shannon N. Westin, MD, MPH, FACOG, Associate Professor in the Department of Gynecologic Oncology and Reproductive Medicine, Division of Surgery, and Director of Early Drug Development at The University of Texas MD Anderson Cancer Center, Houston.
This third of 3 PER Pulse Recaps from this program focuses on how to manage toxicities in patients receiving immunotherapy for cervical cancer. Dr. Westin presented an overview of the types of immune-related adverse events (irAEs) experienced by patients who are taking immune checkpoint inhibitors (ICPis) and how she manages some of the commonly encountered toxicities. During her presentation, she made several key points:

  • Because ICPis create an autoimmune-like state, any normal tissues can be attacked by the immune system. This is illustrated by the wide range of AEs experienced by patients taking ICPis, including gastrointestinal toxicities (mucositis, colitis), skin toxicities (rash), pulmonary toxicities (pneumonitis), hepatic toxicities (hepatitis), endocrine toxicities (thyroiditis, hypothyroidism), and ocular toxicities (uveitis).
  • Most irAEs have a median onset between 6 and 10 weeks after treatment initiation, but skin toxicities are typically the earliest to develop. The timing of irAEs varies, however, and can even arise after treatment discontinuation.
  • Although management of irAEs varies depending on the specific irAE encountered, steroids such as methylprednisolone are generally used as a first-line treatment for most irAEs. If those are not effective, additional immunosuppressive agents, such as infliximab or mycophenolate mofetil, can be used.

Following Dr. Westin’s presentation, Dr. Duska presented a case of one of her patients who had received nearly 1 year of pembrolizumab as second-line therapy for cervical cancer before transitioning to a treatment holiday. She described how she diagnosed this patient with pneumonitis, with the help of a Pulmonary Medicine consult, and how she treated this patient successfully with steroids.

Off-Label Disclosure and Disclaimer

This CME activity may or may not discuss investigational, unapproved, or off-label use of drugs. Participants are advised to consult prescribing information for any products discussed. The information provided in this CME activity is for continuing medical and nursing education purposes only, and is not meant to substitute for the independent clinical judgment of a physician relative to diagnostic, treatment, or management options for a specific patient’s medical condition. The opinions expressed in the content are solely those of the individual faculty members and do not reflect those of PER®.


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