Investigators Discuss the Optimal Clinical Care of Patients with HER2-Positive Gynecologic Cancers — Symposium Video Proceedings

Faculty

TARGET AUDIENCE
This activity is intended for gynecologic oncologists, medical oncologists, gynecologists and other healthcare providers involved in the treatment of gynecologic cancers.

LEARNING OBJECTIVES

• Appreciate the prevalence and relevance of HER2 amplification/overexpression in various gynecologic cancers, and consider the implications for biomarker assessment and clinical management.
• Evaluate published research findings with established HER2-targeted therapies for patients with HER2-positive gynecologic cancers, and assess the current role of various agents and regimens.
• Recall available data with novel HER2-targeted antibody-drug conjugates for HER2-positive ovarian, endometrial and cervical cancers, and optimally integrate these agents into the care of appropriately selected patients.
• Appraise the side effects associated with various HER2-directed therapies commonly employed in the care of patients with gynecologic cancers, and use this information to develop supportive therapeutic plans for those undergoing treatment with these agents or regimens.
• Recall the design of ongoing clinical trials evaluating novel HER2-directed agents and strategies for advanced HER2-positive gynecologic cancers, and counsel appropriately selected patients about availability and participation.

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CREDIT DESIGNATION STATEMENT
Research To Practice designates this enduring material for a maximum of 1.75 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

AMERICAN BOARD OF INTERNAL MEDICINE (ABIM) — MAINTENANCE OF CERTIFICATION (MOC)
Successful completion of these CME activities, which includes participation in the evaluation component and a post-test, enables the participant to earn up to 1.75 (video) Medical Knowledge MOC points in the American Board of Internal Medicine’s (ABIM) Maintenance of Certification (MOC) program. Participants will earn MOC points equivalent to the amount of CME credits claimed for each activity. It is the CME activity provider’s responsibility to submit participant completion information to ACCME for the purpose of granting ABIM MOC credit.

Please note, this program has been specifically designed for the following ABIM specialty: medical oncology.

AMERICAN BOARD OF SURGERY (ABS) — CONTINOUS CERTIFICATION (CC)
Successful completion of these CME activities, which includes participation in the evaluation component, enables the learner to earn credit toward the CME and Self-Assessment requirement(s) of the American Board of Surgery’s Continuous Certification program. It is the CME activity provider’s responsibility to submit participant completion information to ACCME for the purpose of granting ABS credit.

Please note, this program has been specifically designed for the following ABS practice area: complex general surgical oncology. 

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HOW TO USE THIS CME ACTIVITY
This CME activity consists of a video component. To receive credit, the participant should review the CME information, watch the video, complete the post-test with a score of 80% or better and fill out the evaluation located at ResearchToPractice.com/SGO25HER2PosGyn/Video/CME.

CONTENT VALIDATION AND DISCLOSURES
Research To Practice (RTP) is committed to providing its participants with high-quality, unbiased and state-of-the-art education and adheres to the ACCME’s Standards for Integrity and Independence in Accredited Continuing Education. Any individuals in a position to control the content of an accredited continuing education activity, including faculty, planners, reviewers and others, are required to disclose all relevant financial relationships with ineligible entities (commercial interests). All relevant conflicts of interest have been mitigated prior to the commencement of these activities. In addition, all activity content is reviewed by RTP scientific staff and an external, independent physician reviewer for fair balance, scientific objectivity of studies referenced and patient care recommendations.

FACULTY — The following faculty reported relevant financial relationships with ineligible entities:

Kathleen N Moore, MD, MS
Deputy Director
Virginia Kerley Cade Chair in Developmental Therapeutics
Co-Director, Cancer Therapeutics Program
Stephenson Cancer Center at the University of Oklahoma HSC
Associate Director, GOG Partners
Board of Directors, GOG Foundation
Board of Directors, ASCO
Oklahoma City, Oklahoma

Advisory Committees: Aadi Bioscience, AbbVie Inc, AstraZeneca Pharmaceuticals LP, BioNTech SE, Blueprint Medicines, Caris Life Sciences, Corcept Therapeutics, Daiichi Sankyo Inc, Duality Biologics, Eisai Inc, Genentech, a member of the Roche Group, GSK, ImmunoGen Inc, Janssen Biotech Inc, Lilly, Merck, Mersana Therapeutics Inc, Novartis, Regeneron Pharmaceuticals Inc, Schrödinger, Takeda Pharmaceuticals USA Inc, Verastem Inc, Zentalis Pharmaceuticals, Zymeworks Inc; Contracted Research: Allarity Therapeutics, Daiichi Sankyo Inc, GSK, ImmunoGen Inc, Schrödinger, Verastem Inc; Data and Safety Monitoring Boards/Committees: Bicycle Therapeutics.

Alessandro D Santin, MD
Professor
Department of Obstetrics and Gynecology
Co-Chief, Gynecologic Oncology
Yale University School of Medicine
New Haven, Connecticut

Advisory Committees: Daiichi Sankyo Inc, Eisai Inc, Gilead Sciences Inc, Merck, Pfizer Inc, R-Pharm US; Contracted Research: Boehringer Ingelheim Pharmaceuticals Inc, Genentech, a member of the Roche Group, Gilead Sciences Inc, Merck, R-Pharm US, Synthon, Tesaro, A GSK Company, Verastem Inc.

MODERATOR
David M O’Malley, MD
Director and Professor
Division of Gynecologic Oncology in Obstetrics and Gynecology
John G Boutselis Chair in Gynecologic Oncology
The Ohio State University and The James Comprehensive Cancer Center
Columbus, Ohio

Advisory Committees and Consulting Agreements: AbbVie Inc, AstraZeneca Pharmaceuticals LP, Corcept Therapeutics, Duality Biologics, Genmab US Inc, GSK, Merck, MSD, Regeneron Pharmaceuticals Inc, Seagen Inc, Sumitomo Dainippon Pharma Oncology Inc, Sutro Biopharma, Verastem Inc; Contracted Research: AbbVie Inc, Adaptimmune, Advaxis Inc, Agenus Inc, Alkermes, Aravive Inc, Arcus Biosciences, Arquer Diagnostics, AstraZeneca Pharmaceuticals LP, Atossa Therapeutics, BeiGene Ltd, Bristol Myers Squibb, Cardiff Oncology, Celcuity, Clovis Oncology, Corcept Therapeutics, Deciphera Pharmaceuticals Inc, Duality Biologics, Eisai Inc, Elevar Therapeutics, EMD Serono Inc, Exelixis Inc, Genelux Corporation, Genentech, a member of the Roche Group, Genmab US Inc, GSK, ImmunoGen Inc, Imvax Inc, Incyte Corporation, InterVenn Biosciences, InxMed, Iovance Biotherapeutics, Janssen Biotech Inc, Jazz Pharmaceuticals Inc, Karyopharm Therapeutics, Laekna Therapeutics, Leap Therapeutics Inc, Luzsana Biotechnology, Merck, Mersana Therapeutics Inc, MSD, Myriad Genetic Laboratories Inc, Novartis, Novocure Inc, Onconova Therapeutics Inc, OncoQuest Inc, Pfizer Inc, Predictive Oncology Inc, Prelude Therapeutics, Regeneron Pharmaceuticals Inc, Replimune, Roche Laboratories Inc, R-Pharm US, Rubius Therapeutics, Seagen Inc, Sorrento Therapeutics, Sumitomo Dainippon Pharma Oncology Inc, Sutro Biopharma, Tarveda Therapeutics, Tesaro, A GSK Company, Toray Industries Inc, Trillium Therapeutics Inc, Umoja Biopharma, VBL Therapeutics, Verastem Inc, Vincerx Pharma, Xencor, Zentalis Pharmaceuticals; Nonrelevant Financial Relationships: Amarex Clinical Research, GOG Foundation, Ludwig Institute for Cancer Research Ltd, National Cancer Institute, NRG Oncology, RTOG Foundation, SWOG.

RESEARCH TO PRACTICE CME PLANNING COMMITTEE MEMBERS, STAFF AND REVIEWERS — Planners, scientific staff and independent reviewers for Research To Practice have no relevant conflicts of interest to disclose.

These educational activities contain discussion of published and/or investigational uses of agents that are not indicated by the Food and Drug Administration. Research To Practice does not recommend the use of any agent outside of the labeled indications. Please refer to the official prescribing information for each product for discussion of approved indications, contraindications and warnings. The opinions expressed are those of the presenters and are not to be construed as those of the publisher or grantors.

These activities are supported by educational grants from AstraZeneca Pharmaceuticals LP and Daiichi Sankyo Inc.

Release date: April 2025
Expiration date: April 2026

After completing the post-test, learners may download and review the answers here in order to identify further areas of study.

Dr Santin

Black JD et al. PIK3CA oncogenic mutations represent a major mechanism of resistance to trastuzumab in HER2/neu overexpressing uterine serous carcinomas. Br J Cancer 2015;113(7):1020-6. Abstract

Buza N. HER2 testing in endometrial serous carcinoma: Time for standardized pathology practice to meet the clinical demand. Arch Pathol Lab Med 2021;145(6):687-91. Abstract

Cancer Genome Atlas Research Network. Integrated genomic and molecular characterization of cervical cancer. Nature 2017;543(7645):378-84. Abstract

Cancer Genome Atlas Research Network. Integrated genomic analyses of ovarian carcinoma. Nature 2011;474(7353):609-15. Abstract

English DP et al. T-DM1, a novel antibody-drug conjugate, is highly effective against primary HER2 overexpressing uterine serous carcinoma in vitro and in vivo. Cancer Med 2014;3(5):1256-65. Abstract

Levine DA et al. Integrated genomic characterization of endometrial carcinoma. Nature 2013;497(7447):67-73. Abstract

Meric-Bernstam F et al. Efficacy and safety of trastuzumab deruxtecan in patients with HER2-expressing solid tumors: Primary results from the DESTINY-PanTumor02 phase II trial. J Clin Oncol 2024;42(1):47-58. Abstract

 

Dr O’Malley

Ahn ER et al. Pertuzumab plus trastuzumab in patients with endometrial cancer with ERBB2/3 amplification, overexpression, or mutation: Results from the TAPUR study. JCO Precis Oncol 2023:7. Abstract

Bardia A et al. Trastuzumab deruxtecan after endocrine therapy in metastatic breast cancer. N Engl J Med 2024;391(22):2110-22. Abstract

Curigliano G et al. Trastuzumab deruxtecan (T-DXd) vs physician’s choice of chemotherapy (TPC) in patients (pts) with hormone receptor-positive (HR+), human epidermal growth factor receptor 2 (HER2)-low or HER2-ultralow metastatic breast cancer (mBC) with prior endocrine therapy (ET): Primary results from DESTINY-Breast06 (DB-06). ASCO 2024;LBA1000.

Fader AN et al. Randomized phase II trial of carboplatin-paclitaxel compared with carboplatin-paclitaxel-trastuzumab in advanced (stage III-IV) or recurrent uterine serous carcinomas that overexpress Her2/Neu (NCT01367002): Updated overall survival analysis. Clin Cancer Res 2020;26(15):3928-35. Abstract

Fader AN et al. Randomized phase II trial of carboplatin-paclitaxel versus carboplatin-paclitaxel-trastuzumab in uterine serous carcinomas that overexpress human epidermal growth factor receptor 2/neu. J Clin Oncol 2018;36(20):2044-51. Abstract

Hasegawa K et al. Efficacy and safety of trastuzumab deruxtecan in HER2-expressing uterine carcinosarcoma (STATICE trial, NCCH1615): A multicenter, phase II clinical trial. ESMO 2021;Abstract 813P.

Jhaveri KL et al. Ado-trastuzumab emtansine (T-DM1) in patients with HER2-amplified tumors excluding breast and gastric/gastroesophageal junction (GEJ) adenocarcinomas: Results from the NCI-MATCH trial (EAY131) subprotocol Q. Ann Oncol 2019;30(11):1821-30. Abstract

Lee J-Y et al. Efficacy and safety of trastuzumab deruxtecan in patients with HER2-expressing solid tumors: Results from the cervical, endometrial, and ovarian cancer cohorts of the DESTINY-PanTumor02 study. International Gynecological Cancer Society 2023;Abstract 1550.

Makker V et al. Efficacy and safety of trastuzumab deruxtecan among patients with HER2-expressing solid tumors: Biomarker and subgroup analyses from the cervical, endometrial, and ovarian cancer cohorts of the DESTINY-PanTumor02 study. SGO 2024;Abstract 04.

Modi S et al. Trastuzumab deruxtecan (T-DXd) versus treatment of physician’s choice (TPC) in patients (pts) with HER2-low unresectable and/or metastatic breast cancer (mBC): Updated survival results of the randomized, phase III DESTINY-Breast04 study. ESMO 2023;Abstract 376O.

Modi S et al. Trastuzumab deruxtecan in previously treated HER2-low advanced breast cancer. N Engl J Med 2022;387(1):9-20. Abstract

Modi S et al. Trastuzumab deruxtecan (T-DXd) versus treatment of physician’s choice (TPC) in patients (pts) with HER2-low unresectable and/or metastatic breast cancer (mBC): Results of DESTINY-Breast04, a randomized, phase 3 study. ASCO 2022;Abstract LBA3.

Moore K et al. DB-1303, a HER2-targeting ADC, for patients with advanced/metastatic endometrial cancer: Preliminary clinical results from an ongoing phase 1/2a trial (NCT05150691). ESGO 2023;Abstract 430.

Nakamura Y et al. Tucatinib and trastuzumab for previously treated human epidermal growth factor receptor 2-positive metastatic biliary tract cancer (SGNTUC-019): A phase II basket study. J Clin Oncol 2023;41(36):5569-78. Abstract

Nishikawa T et al. Trastuzumab deruxtecan for human epidermal growth factor receptor 2-expressing advanced or recurrent uterine carcinosarcoma (NCCH1615): The STATICE trial. J Clin Oncol 2023;41(15):2789-99. Abstract

Okines AFC et al. Tucatinib and trastuzumab in HER2-mutated metastatic breast cancer: A phase 2 basket trial. Nat Med 2025;31(3):909-16. Abstract

 

Dr Moore

Abelman RO et al. Association of pretreatment chest CT abnormalities with trastuzumab deruxtecan–associated pneumonitis. ASCO 2023;Abstract 1106.

Nguyen TD et al. Mechanisms of ADC toxicity and strategies to increase ADC tolerability. Cancers (Basel) 2023;15(3):713. Abstract

Pedersini R et al. Gastrointestinal toxicity of antibody drug conjugates (ADCs) in metastatic breast cancer: A pooled analysis. Clin Breast Cancer 2024;24(5):411-20. Abstract

Rugo H et al. Pooled analysis of trastuzumab deruxtecan (T-DXd) retreatment (RTx) after recovery from grade (Gr) 1 interstitial lung disease/pneumonitis (ILD). ESMO Breast Cancer 2024;Abstract 267MO.

Rugo H et al. Optimizing treatment management of trastuzumab deruxtecan in clinical practice of breast cancer. ESMO Open 2022;7(4). Abstract

Swain SM et al. Multidisciplinary clinical guidance on trastuzumab deruxtecan (T-DXd)-related interstitial lung disease/pneumonitis-focus on proactive monitoring, diagnosis, and management. Cancer Treat Rev 2022;106:102378. Abstract

Tarantino P, Tolaney SM. Detecting and managing T-DXd-related interstitial lung disease: The five “S” rules. JCO Oncol Pract 2023;19(8):526-27. Abstract

Zhu Y et al. Treatment-related adverse events of antibody-drug conjugates in clinical trials: A systematic review and meta-analysis. Cancer 2023;129(2):283-95. Abstract