In recent years, several antibody-drug conjugates (ADCs) were approved across a variety of solid tumors. This presents challenges when managing a multitude of treatment-related adverse events, some of which may lead clinicians into unfamiliar territory. This series of educational activities focuses on appropriate management of ADC-related adverse events in breast, lung, gastric, and bladder cancers.
HER3-Directed ADCs in Breast Cancer
A Deep Dive into the Management of AEs Associated with ADCs
HER3-Directed ADCs in Breast Cancer
HER3-Directed ADCs in Breast Cancer
HER3-Directed ADCs in Breast Cancer
Welcome to CME on ReachMD. This episode is part of our MinuteCME curriculum and is titled “HER3-Directed ADCs in Breast Cancer”.
Prior to beginning the activity, please be sure to review the faculty and commercial support disclosure statements as well as the learning objectives.
This is CME on ReachMD, and I'm Dr. Sara Hurvitz, Professor of Medicine and Medical Oncologist at UCLA.
The treatment of breast cancer has been revolutionized by the development of therapies that specifically target antigens that are expressed uniquely or at a high level on the surface of tumors. Antibody-drug conjugates, which selectively deliver chemotherapy to tumor antigen-overexpressing cancer cells, have demonstrated significant antitumor efficacy in HER2-positive breast cancer and triple-negative breast cancer.
The development of ADCs, or antibody-drug conjugates, is now expanding to other tumor antigens. For example, to HER3, making this field extremely exciting. While data are quite promising, there are unique side effects to be aware of as we see these agents enter later-phase clinical trials.
One agent that is targeting HER3 is patritumab deruxtecan. This HER3-targeted ADC is delivering a topoisomerase-1 inhibitor cytotoxic payload to HER3-expressing cancer cells. This agent is currently being evaluated in early phase clinical trials, including studies in non-small cell lung cancer and breast cancer.
A phase 2 trial evaluating this agent in lung cancer called HERTHENA-Lung01, has been reported showing early evidence of efficacy and also giving us insights into the safety profile of this drug. Toxicities from this agent included GI-related side effects such as nausea and vomiting, as well as laboratory abnormalities such as cytopenias and alterations in liver enzymes. Fatigue has also been reported.
In terms of breast cancer, this drug is also being evaluated in hormone receptor-positive metastatic breast cancer. The SOLTI-1805 TOT-HER3 clinical trial evaluated patritumab deruxtecan in patients with hormone receptor-positive HER2-negative metastatic breast cancer. In this study, 30 patients were treated, and clinical responses were noted. The side effect profile included nausea, fatigue, abdominal pain, alopecia, as well as cytopenias. In addition, alterations in liver enzymes were noted, including one grade 3 event.
It may be important for us to evaluate the safety of these agents utilizing a multidisciplinary team approach to managing these side effects profiles. Moreover, it's going to be important for us to follow the patient-reported outcomes from larger-phase clinical trials looking at patritumab deruxtecan or other HER3-targeted ADCs.
In summary, this is a very exciting field as we begin to see ADCs targeting antigens that are outside of HER2 or TROP-2. Looking at drugs like TROP-3, targeted ADCs such as patritumab deruxtecan, we are beginning to see proof of principle efficacy, as well as an early glimpse into the safety profile of these agents.
Thank you so much for your time today. I hope this has been helpful.
You have been listening to CME on ReachMD. This activity is provided by Prova Education and is part of our MinuteCME curriculum.
To receive your free CME credit, or to download this activity, go to ReachMD.com/Prova. Thank you for listening.
Disclosure of Conflicts of Interest
In accordance with the ACCME Standards for Integrity and Independence, Global Learning Collaborative (GLC) requires that individuals in a position to control the content of an educational activity disclose all relevant financial relationships with any ineligible company. GLC mitigates all conflicts of interest to ensure independence, objectivity, balance, and scientific rigor in all its educational programs.
Jaffer A. Ajani, MD
Professor, Department of Gastrointestinal Medical Oncology
Division of Cancer Medicine
The University of Texas MD Anderson Cancer Center
Research: Daiichi Sankyo
Consulting Fees: AstraZeneca, Daiichi Sankyo
Justin Gainor, MD
Director, Center for Thoracic Cancers
Director, Targeted Immunotherapy
Massachusetts General Hospital
Contracted Research: Adaptimmune, Alexo, Ariad/Takeda, Array, BMS, Blueprint, Genentech/ Roche, Jounce, Merck, Moderna, Novartis, Scholar Rock, and Tesaro
Consulting Fees: Agios, Amgen, Ariad/Takeda, Array, AstraZeneca, BMS, Clovis Oncology, EMD Serono, Genentech, Glyde Bio, Helsinn, Incyte, Jounce, Karyopharm, Loxo, Merck, Mirati, Novartis, Oncorus, Pfizer, and Regeneron
Sara Hurvitz, MD
Professor of Medicine
David Geffen School of Medicine, UCLA
Santa Monica, CA
Contracted Research: Ambrx, Amgen, Arvinas, AstraZeneca, Bayer, CytomX, Daiichi Sankyo, Dignitana, Eli Lilly, Genentech/Roche, Gilead, GSK, Immunomedics, MacroGenics, Novartis, OBI Pharma, Orinove, Pfizer, Phoenix Molecular Designs, Ltd., Pieris, PUMA, Radius, Sanofi, Seattle Genetics/Seagen, Zymeworks
Preclinical Work: Ambrx, Samumed
National/International PI: Daiichi Sankyo, GNE/Roche, Novartis, SeaGen
Steering Committee: Daiichi-Sankyo/AZ, GNE/Roche, Lilly, Novartis, Sanofi
Uncompensated consulting/ad boards: 4DPharma, Ambrx, Amgen, Artios, Arvinas, Biotheranostics, Daiichi Sankyo, Dantari, Eli Lilly, Genentech/Roche, Immunomedics, MacroGenics, NKMax, Novartis, Pieris, Pyxis, Seagen
Gopa Iyer, MD
Associate Attending Physician
Section Head, Urothelial Carcinoma
Memorial Sloan Kettering Cancer Center
New York, NY
Research: Aadi Biosciences, Janssen, Mirati Therapeutics, SeaGen
Consulting Fees: Basilea, EMD Serono, Flare Therapeutics, Gilead, Loxo Oncology, Silverback Therapeutics, The Lynx Group
- Jorge Bacigalupo, PSM has nothing to disclose.
- Cindy Davidson has nothing to disclose.
- Ann Early has nothing to disclose.
- Nicole Fox, DNP, MSN-Ed., RN, OCN has nothing to disclose.
- Anna Trentini has nothing to disclose.
After participating in this educational activity, participants should be better able to:
- Describe the components of an antibody-drug conjugate (ADC) that may cause adverse events (AEs)
- Recognize AEs that lead to treatment interruption or discontinuation
- Recommend an approach for managing the key AEs associated with ADCs
- Design a mitigation plan for AEs in patients at high risk for ADC-related AEs
This activity is designed to meet the educational needs of medical oncologists, pulmonologists, urologists, pathologists, oncology nurse practitioners, physician assistants, oncology nurses, oncology pharmacists, and other HCPs managing patients with solid tumors.
Accreditation and Credit Designation Statements
In support of improving patient care, Global Learning Collaborative (GLC) is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC) to provide continuing education for the healthcare team.
Global Learning Collaborative (GLC) designates this Enduring activity for a maximum of 1 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.
Global Learning Collaborative (GLC) designates this activity for 1 hour of nursing contact hours. Nurses should claim only the credit commensurate with the extent of their participation in the activity.
Global Learning Collaborative (GLC) has been authorized by the American Academy of PAs (AAPA) to award AAPA Category 1 CME credit for activities planned in accordance with AAPA CME Criteria. This activity is designated for 1 AAPA Category 1 CME credits. Approval is valid until 06/30/2023. PAs should claim only the credit commensurate with the extent of their participation in the activity.
This curriculum has been approved for 1.0 contact hours 0.1 CEUs by Global Learning Collaborative (GLC). GLC is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education. The Universal Activity Number for this program is UAN JA0006235-0000-22-029-H01-P. This learning activity is enduring-based. Your CE credits will be electronically submitted to the NABP upon successful completion of the activity. Pharmacists with questions can contact NABP customer service (firstname.lastname@example.org).
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This activity is supported by independent educational grants from AstraZeneca and Daiichi Sankyo.
The views and opinions expressed in this educational activity are those of the faculty and do not necessarily represent the views of GLC and Prova Education. This presentation is not intended to define an exclusive course of patient management; the participant should use his/her clinical judgment, knowledge, experience, and diagnostic skills in applying or adopting for professional use any of the information provided herein. Any procedures, medications, or other courses of diagnosis or treatment discussed or suggested in this activity should not be used by clinicians without evaluation of their patients’ conditions and possible contraindications or dangers in use, review of any applicable manufacturer’s product information, and comparison with recommendations of other authorities. Links to other sites may be provided as additional sources of information. Once you elect to link to a site outside of Prova Education you are subject to the terms and conditions of use, including copyright and licensing restriction, of that site.
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