Expert Second Opinion: Investigators Provide Perspectives on the Management of HER2-Positive Gynecologic Cancers — Microlearning Activity 2

Faculty

TARGET AUDIENCE
This activity is intended for medical oncologists, hematology-oncology fellows and other healthcare providers 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.
• 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 0.75 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 0.75 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) — CONTINUOUS CERTIFICATION (CC)
Successful completion of this CME activity, which includes participation in the evaluation component 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.

PRIVACY POLICY
Personal information and data sharing: Research To Practice aggregates deidentified user data for program-use analysis, program development, activity planning and site improvement. We may provide aggregate and deidentified data to third parties, including commercial supporters. We do not share or sell personally identifiable information to any unaffiliated third parties or commercial supporters. Please see our privacy policy at ResearchToPractice.com/Privacy-Policy for more information.

HOW TO USE THIS CME ACTIVITY
To receive credit for this activity, the participant should review the CME information, watch the video, review the slide presentation, 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:

Dr Liu — 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. Dr Slomovitz — Consulting Agreements: Aadi Bioscience, AbbVie Inc, AstraZeneca Pharmaceuticals LP, BeOne, BioNTech SE, Corcept Therapeutics Inc, Daiichi Sankyo Inc, Eisai Inc, Genmab US Inc, GSK, Incyte Corporation, Karyopharm Therapeutics, Merck; Data and Safety Monitoring Boards/Committees: Genelux Corporation.

CONSULTING CLINICAL INVESTIGATORS
Professor Jonathan A Ledermann, MD — 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, Ascendis Pharma, Corcept Therapeutics Inc, Day One Biopharmaceuticals, GSK, Kaida BioPharma, Merck, NextCure, Whitehawk Therapeutics; Data and Safety Monitoring Boards/Committees: AstraZeneca Pharmaceuticals LP, 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
Dr O’Malley — 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: September 2026
Expiration date: September 2027

A phase 3, multicenter, randomized, open-label trial of trastuzumab deruxtecan versus standard of care chemotherapy with or without radiotherapy as adjuvant treatment for HER2-expressing (IHC 3+/2+) endometrial cancer (DESTINY-Endometrial02/GOG-3122/ENGOT-en30/GINECO). NCT07022483

A phase 3, open-label, multicenter, randomized trial of trastuzumab deruxtecan with bevacizumab versus bevacizumab monotherapy as first-line maintenance therapy in HER2-expressing ovarian cancer (DESTINY-Ovarian01/ENGOT-ov89/GEICO144-O/GOG-3112/APGOT-OV13). NCT06819007

A phase II/III study of paclitaxel/carboplatin alone or combined with either trastuzumab and hyaluronidase-oysk (HERCEPTIN HYLECTA) or pertuzumab, trastuzumab, and hyaluronidase-zzxf (PHESGO) in HER2 positive, stage I-IV endometrial serous carcinoma or carcinosarcoma. NCT05256225

A phase III, randomized, multi-site, open-label trial of BNT323/DB-1303 versus investigator’s choice of chemotherapy in previously treated patients with HER2-expressing recurrent endometrial cancer. NCT06340568

de Boer SM et al. Adjuvant chemoradiotherapy versus radiotherapy alone in women with high-risk endometrial cancer (PORTEC-3): Patterns of recurrence and post-hoc survival analysis of a randomised phase 3 trial. Lancet Oncol 2019;20(9):1273-85. Abstract

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

Garg AD et al. Molecular and translational classifications of DAMPs in immunogenic cell death. Front Immunol 2015;6:588. Abstract

Halle MK et al. HER2 expression patterns in paired primary and metastatic endometrial cancer lesions. Br J Cancer 2018;118(3):378-87. Abstract

Krakstad C et al. Frequency of ERBB2-low expression in endometrial cancer. JAMA Oncol 2024;10(11):1587-8. Abstract

Li TK, Liu LF. Tumor cell death induced by topoisomerase-targeting drugs. Annu Rev Pharmacol Toxicol 2001;41:53-77. Abstract

Lin S et al. DB-1303, a HER2-targeting ADC with a novel DNA topoisomerase I inhibitor, demonstrates a promising safety profile and anti-tumor efficacy with differentiation from DS-8201a. Eur J Cancer 2022;174(Suppl 1):S91. 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.

Matei DE et al. Long-term follow-up and overall survival in NRG258, a randomized phase III trial of chemoradiation versus chemotherapy for locally advanced endometrial carcinoma. J Clin Oncol 2025;43(9):1055-60. 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

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

Post CCB et al. Adjuvant chemoradiotherapy versus radiotherapy alone in women with high-risk endometrial cancer (PORTEC-3): 10-year clinical outcomes and post-hoc analysis by molecular classification from a randomised phase 3 trial. Lancet Oncol 2025;26(10):1370-81. Abstract

Pothuri B et al. Trastuzumab pamirtecan (DB-1303/BNT323) in patients with previously treated HER2-expressing advanced/metastatic endometrial cancer: First global clinical phase 2 data. Gynecol Oncol 2026;208(Suppl):S32. 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.

Van Gorp T et al. ENGOT-en11/GOG-3053/KEYNOTE-B21: A randomised, double-blind, phase III study of pembrolizumab or placebo plus adjuvant chemotherapy with or without radiotherapy in patients with newly diagnosed, high-risk endometrial cancer. Ann Oncol 2024;35(11):968-80. Abstract