Investigators Provide Perspectives on the Management of HER2-Positive Gynecologic Cancers — Symposium Video Proceedings

Faculty

TARGET AUDIENCE
This activity is intended for medical oncologists, hematologists, hematology-oncology fellows, radiation oncologists, surgeons and other allied healthcare professionals involved in the treatment of gynecologic cancers.

LEARNING OBJECTIVES

• Appreciate the prevalence and clinical relevance of human epidermal growth factor receptor 2 (HER2) amplification and 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 HER2-targeted antibody-drug conjugates in the treatment of 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 for gynecologic cancers, and use this information to develop supportive management plans for patients.
• Recall the design of ongoing clinical trials evaluating novel HER2-directed agents and strategies for advanced HER2-positive gynecologic cancers, and appropriately counsel patients about availability and participation.

ACCREDITATION STATEMENT
Research To Practice is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.

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 this CME activity, which includes participation in the evaluation component and a post-test, enables the participant to earn up to 1.75 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 the 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 this CME activity, which includes participation in the evaluation components and a post-test, 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
To receive credit for this activity, 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.

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 financial relationships have been mitigated prior to the commencement of this activity. 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:

Joyce F Liu, MD, MPH

Consulting Agreements: AbbVie Inc, AstraZeneca Pharmaceuticals LP, Bristol Myers Squibb, Cullinan Therapeutics, Daiichi Sankyo Inc, Eisai Inc, Genmab US Inc, GSK, Loxo Oncology Inc, a wholly owned subsidiary of Eli Lilly & Company, Merck, Revolution Medicines Inc, SystImmune Inc.

Brian M Slomovitz, MD

Advisory Committees: Aadi Bioscience, AstraZeneca Pharmaceuticals LP, BeOne, Daiichi Sankyo Inc, Eisai Inc, Genmab US Inc, Gilead Sciences Inc, GSK, Immunocore, Incyte Corporation, Karyopharm Therapeutics, Merck, Novocure Inc, Regeneron Pharmaceuticals Inc, Seagen Inc; Consulting Agreements: Aadi Bioscience, AstraZeneca Pharmaceuticals LP, Genmab US Inc, GSK, Karyopharm Therapeutics, Seagen Inc; Data and Safety Monitoring Boards/Committees: Genelux.

CONSULTING CLINICAL INVESTIGATORS
Professor Jonathan A Ledermann — Advisory Committees: AbbVie Inc, AstraZeneca Pharmaceuticals LP, Flindr, GSK, ImmunoGen Inc, MSD, Novocure Inc; Consulting Agreements: AbbVie Inc, GSK; Data and Safety Monitoring Boards/Committees: AstraZeneca Pharmaceuticals LP, Daiichi Sankyo Inc, Sutro Biopharma, Zentalis Pharmaceuticals; Speakers Bureaus: AstraZeneca Pharmaceuticals LP, GSK, Medison Pharmaceuticals, MSD. Ursula Matulonis, MD — Advisory Committees: AbbVie Inc, AstraZeneca Pharmaceuticals LP, Daiichi Sankyo Inc, Day One Biopharmaceuticals, GSK, NextCure, Novartis, Tango Therapeutics; Consulting Agreements: Whitehawk Therapeutics; Data and Safety Monitoring Boards/Committees: Daiichi Sankyo Inc, MacroGenics Inc, Mural Oncology Inc, Symphogen A/S. Angeles Alvarez Secord, MD, MHSc — Advisory Committees: AbbVie Inc, AstraZeneca Pharmaceuticals LP, Daiichi Sankyo Inc, Foundation Medicine, Genmab US Inc, Gilead Sciences Inc, GSK, HistoSonics, Medtronic Inc, Merck; Clinical Trial Steering Committees: Genmab US Inc, OncoQuest Inc; Consulting Agreements: GSK, Merck; Contracted Research: AbbVie Inc, Aravive Inc, AstraZeneca Pharmaceuticals LP, Canaria Bio Inc, Daiichi Sankyo Inc, Ellipses Pharma, Genentech, a member of the Roche Group, Genmab US Inc, GSK, ImmunoGen Inc, Karyopharm Therapeutics, Merck, Mersana Therapeutics Inc, Myriad Genetic Laboratories Inc, OncoQuest Inc, TORL BioTherapeutics, Zentalis Pharmaceuticals; Stock Options/Stock — Public Companies: Stock in Amgen Inc and Johnson & Johnson, divested in June 2024.

MODERATOR
David M O’Malley, MD

Consulting Agreements — Personal Fees (Consult and/or Advisory Boards): AbbVie Inc, AstraZeneca Pharmaceuticals LP, BeOne,Corcept Therapeutics Inc, Daiichi Sankyo Inc, Duality Biologics, Genmab US Inc, GSK, Lilly, Merck, MSD, Novocure Inc, Pfizer Inc, Regeneron Pharmaceuticals Inc, Verastem Inc, Zentalis Pharmaceuticals; Contracted Research (Institution Received Funds for Research): AbbVie Inc, Advaxis Inc, Agenus Inc, Alkermes, Aravive Inc, Arcus Biosciences, AstraZeneca Pharmaceuticals LP, BeOne, Bristol Myers Squibb, Deciphera Pharmaceuticals Inc, Eisai Inc, EMD Serono Inc, Exelixis Inc, F Hoffmann-La Roche Ltd, Genentech, a member of the Roche Group, Genmab US Inc, GSK, ImmunoGen Inc, Incyte Corporation, Iovance Biotherapeutics, Karyopharm Therapeutics, Leap Therapeutics Inc, Merck, Mersana Therapeutics Inc, MSD, Novartis, Novocure Inc, OncoC4, OncoQuest Inc, Pfizer Inc, pharmaand GmbH, Predictive Oncology Inc, Prelude Therapeutics, Regeneron Pharmaceuticals Inc, Seagen Inc, Sumitomo Pharma America, Sutro Biopharma, Tesaro, A GSK Company, Verastem Inc; Data and Safety Monitoring Boards/Committees: Frantz Viral Therapeutics.

EDITOR — Dr Love is president and CEO of Research To Practice. Research To Practice receives funds in the form of educational grants to develop CME activities from the following companies: Aadi Bioscience, AbbVie Inc, ADC Therapeutics, Agendia Inc, Alexion Pharmaceuticals, Amgen Inc, Array BioPharma Inc, a subsidiary of Pfizer Inc, Arvinas, Astellas, AstraZeneca Pharmaceuticals LP, Aveo Pharmaceuticals, Bayer HealthCare Pharmaceuticals, BeOne, Biotheranostics Inc, A Hologic Company, Black Diamond Therapeutics Inc, Blueprint Medicines, Boehringer Ingelheim Pharmaceuticals Inc, Bristol Myers Squibb, Catalyst Pharmaceuticals Inc, Celcuity, Clovis Oncology, Coherus BioSciences, Corcept Therapeutics Inc, CTI BioPharma, a Sobi Company, Daiichi Sankyo Inc, Eisai Inc, Elevation Oncology Inc, Exact Sciences Corporation, Exelixis Inc, Genentech, a member of the Roche Group, Genmab US Inc, Geron Corporation, Gilead Sciences Inc, GSK, Helsinn Therapeutics (US) Inc, ImmunoGen Inc, Incyte Corporation, Ipsen Biopharmaceuticals Inc, Jazz Pharmaceuticals Inc, Johnson & Johnson, Karyopharm Therapeutics, Kite, A Gilead Company, Kura Oncology, Legend Biotech, Lilly, MEI Pharma Inc, Merck, Mersana Therapeutics Inc, Mirati Therapeutics Inc, Mural Oncology Inc, Natera Inc, Novartis, Novartis Pharmaceuticals Corporation on behalf of Advanced Accelerator Applications, Novocure Inc, Nuvalent, Nuvation Bio Inc, Pfizer Inc, Pharmacyclics LLC, an AbbVie Company, Puma Biotechnology Inc, Regeneron Pharmaceuticals Inc, Revolution Medicines Inc, Rigel Pharmaceuticals Inc, R-Pharm US, Sanofi, Seagen Inc, Servier Pharmaceuticals LLC, SpringWorks Therapeutics Inc, Stemline Therapeutics Inc, Sumitomo Pharma America, Summit Therapeutics, Syndax Pharmaceuticals, Taiho Oncology Inc, Takeda Pharmaceuticals USA Inc, TerSera Therapeutics LLC, Tesaro, A GSK Company, and Verastem Inc.

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

This educational activity contains 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.

This activity is supported by educational grants from AstraZeneca Pharmaceuticals LP and Daiichi Sankyo Inc.

Release date: June 2026
Expiration date: June 2027

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

 Dr Liu

Aro K et al. HER2 amplification and HER2 low expression in endometrial carcinoma: Prevalence across molecular, histological and clinicopathological risk groups. BJC Rep 2025;3(1):8. Abstract

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

Ettorre VM et al. Immunohistochemistry, next generation sequencing (NGS), and whole exome sequencing concordance in HER2 testing in uterine serous carcinoma: A retrospective analysis. Gynecol Oncol 2025;202:131-6. Abstract

Fehrenbacher L et al. NSABP B-47/NRG oncology phase III randomized trial comparing adjuvant chemotherapy with or without trastuzumab in high-risk invasive breast cancer negative for HER2 by FISH and with IHC 1+ or 2. J Clin Oncol 2020;38(5):444-53. Abstract

Liu W et al. HER2 expression in cervical squamous cell carcinoma: High prevalence of HER2-low/ultralow and spatiotemporal heterogeneity across tumor evolution. NPJ Precis Oncol 2025;9(1):410. Abstract

Menshikova E et al. Analysis of human epidermal growth factor receptor 2 (HER2) heterogeneity at the protein and gene levels in endometrial cancer: Refining HER2 reporting and HER2-directed therapies. Lab Invest 2025;105(12):104240. Abstract

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

Mosele F et al. Trastuzumab deruxtecan in metastatic breast cancer with variable HER2 expression: The phase 2 DAISY trial. Nat Med 2023;29(8):2110-20. Abstract

Plotkin A et al. Implementation of HER2 testing in endometrial cancer, a summary of real-world initial experience in a large tertiary cancer center. Cancers (Basel) 2024;16(11):2100. Abstract

Zannoni GF et al. HER2 in gynecological malignancies: Bridging the gap between standardized pathological assessment and precision therapy. Crit Rev Oncol Hematol 2026;218:105046. Abstract

 

Dr Slomovitz

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

Makker V et al. Trastuzumab deruxtecan (T-DXd) for pretreated patients (pts) with HER2-expressing solid tumors: DESTINY-PanTumor02 (DP-02) part 1 final analysis. ESMO 2025;Abstract 957P.

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

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.

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

Slomovitz BM et al. A randomized phase III study of first-line (1L) trastuzumab deruxtecan (T-DXd) with rilvegostomig or pembrolizumab in patients with HER2-expressing, mismatch repair-proficient (pMMR), primary advanced or recurrent endometrial cancer (EC): DESTINY-Endometrial01/GOG-3098/ENGOT-EN24. ESMO 2025;Abstract 1223TiP.

 

Dr O’Malley

Azhar M et al. Incidence and risk factors for pneumonitis due to trastuzumab deruxtecan in metastatic breast cancer: A retrospective cohort study. Breast Cancer Res 2025;27(1):197. Abstract

Li BT et al. Trastuzumab deruxtecan in HER2-mutant non-small-cell lung cancer. N Engl J Med 2022;386(3):241-51. Abstract

Meric-Bernstam F et al. Trastuzumab deruxtecan (T-DXd) for pretreated patients (pts) with HER2-expressing solid tumors: Primary analysis from the DESTINY-PanTumor02 (DP-02) study. ESMO 2023;Abstract LBA34.

Natsuhara KH et al. Treatment rechallenge after trastuzumab-deruxtecan–related interstitial lung disease: A multi-institution cohort study. ASCO 2025;Abstract 1015.

Park YH et al. Characterization of the safety profile of trastuzumab deruxtecan by dose: A pooled analysis across DESTINY studies. Oncologist 2025;31(1). Abstract

Powell CA et al. Pooled analysis of drug related interstitial lung disease and/or pneumonitis in nine trastuzumab deruxtecan monotherapy studies. ESMO Open 2022;7(4). Abstract

Rugo HS et al. Pooled analysis of trastuzumab deruxtecan retreatment after recovery from grade 1 interstitial lung disease/pneumonitis. Ann Oncol 2025;36(11):1389-99. Abstract

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