First-Line and Maintenance Therapy for Patients with HER2-Positive Metastatic Breast Cancer — Lecture

Faculty

Professor Doctor Sibylle Loibl

GBG Forschungs GmbH, Neu-Isenburg, Germany

CEO

Goethe University, Frankfurt, Germany

Professor, Innovative Systemic Therapy for Breast Cancer

TARGET AUDIENCE
This activity is intended for medical oncologists, hematology-oncology fellows and other healthcare providers involved in the treatment of breast cancer.

LEARNING OBJECTIVES

• Appraise available clinical research data, recent FDA approvals, current guideline recommendations and best practices to guide the selection of first-line therapy for patients with newly diagnosed HER2-positive metastatic breast cancer (mBC).
• Assess recently presented Phase III data with HER2-directed antibody-drug conjugate therapy as a component of first-line and maintenance therapy, and consider the current role of this novel strategy in the treatment of HER2-positive mBC.
• Appreciate the available research findings with CDK4/6 inhibition in combination with endocrine and anti-HER2 maintenance therapy for patients with hormone receptor-positive, HER2-positive mBC, and use this information to personalize treatment recommendations.
• Recognize available and emerging research findings with HER2-targeted tyrosine kinase inhibitors as a component of maintenance therapy, and reflect on the potential utility of this approach for patients with HER2-positive mBC.

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
Interview: Research To Practice designates this enduring material for a maximum of 1 AMA PRA Category 1 Credit™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Lecture: 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 1 (interview) or 0.75 (lecture) 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) — 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.

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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 (interview, lecture)

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:

Prof Dr Loibl has no relevant financial relationships to disclose.

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: July 2026
Expiration date: July 2027

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

André F et al. Trastuzumab deruxtecan (T-DXd) ± pertuzumab (P) in previously untreated HER2+ metastatic breast cancer (mBC): Clinical efficacy and exploratory subgroup analyses in DESTINY-Breast07. ESMO Targeted Anticancer Therapies Congress 2025;Abstract 7O.

Baselga J et al. Biomarker analyses in CLEOPATRA: A phase III, placebo-controlled study of pertuzumab in human epidermal growth factor receptor 2-positive, first-line metastatic breast cancer. J Clin Oncol 2014;32(33):3753-61. Abstract

Caswell-Jin JL et al. US breast cancer mortality — Reply. JAMA 2024;331(19):1679-80. Abstract

Dieras V et al. HER2CLIMB-05: A phase III study of tucatinib versus placebo in combination with trastuzumab and pertuzumab as first-line maintenance therapy for HER2+ metastatic breast cancer. J Clin Oncol 2026;44(17):1597-607. Abstract

Hamilton E et al. HER2CLIMB-05: A randomized, double-blind, phase 3 study of tucatinib versus placebo in combination with trastuzumab and pertuzumab as maintenance therapy for HER2+ metastatic breast cancer. San Antonio Breast Cancer Symposium 2025;Abstract GS1-01.

Harbeck N et al. Neoadjuvant trastuzumab deruxtecan alone or followed by paclitaxel, trastuzumab, and pertuzumab for high-risk HER2-positive early breast cancer (DESTINY-Breast11): A randomised, open-label, multicentre, phase III trial. Ann Oncol 2026;37(2):166-79. Abstract

Loibl S et al. Trastuzumab deruxtecan (T-DXd) + pertuzumab (P) vs taxane + trastuzumab + pertuzumab (THP) for patients (pts) with HER2+ advanced/metastatic breast cancer (a/mBC): Additional analyses of DESTINY-Breast09 in key subgroups of interest. ESMO 2025;Abstract LBA18.

Metzger O et al. Palbociclib for hormone-receptor-positive, HER2-positive advanced breast cancer. N Engl J Med 2026;394(5):451-62. Abstract

Metzger O et al. Central nervous system outcomes from the phase III PATINA trial (AFT-38). San Antonio Breast Cancer Symposium 2025;Abstract RF4-01.

Swain SM et al. Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA): End-of-study results from a double-blind, randomised, placebo-controlled, phase 3 study. Lancet Oncol 2020;21(4):519-30. Abstract

Tolaney SM et al. Trastuzumab deruxtecan plus pertuzumab for HER2-positive metastatic breast cancer. N Engl J Med 2026;394(6):551-62. Abstract

Tolaney SM et al. Trastuzumab deruxtecan (T-DXd) + pertuzumab (P) vs taxane + trastuzumab + pertuzumab (THP) for first-line (1L) treatment of patients (pts) with human epidermal growth factor receptor 2–positive (HER2+) advanced/metastatic breast cancer (a/mBC): Interim results from DESTINY-Breast09. ASCO 2025;Abstract LBA1008.