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.
TROP2-Directed ADCs in Breast Cancer
TROP2-Directed ADCs in Breast Cancer
Welcome to CME on ReachMD. This episode is part of our MinuteCME curriculum and is titled “TROP2-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 triple-negative breast cancer has dramatically changed recently, not only by the availability of immune checkpoint inhibitors and PARP inhibitors for select patients, but also by the development and approval of the first antibody-drug conjugate [ADC], sacituzumab govitecan, for metastatic triple-negative breast cancer.
This drug selectively delivers chemotherapy to an antigen known as TROP-2, which is expressed on cancer cells.
More recently, early clinical data is emerging relating to the antitumor activity of another TROP-2-targeted ADC, datopotamab deruxtecan, or Dato-DXd. While these agents have both demonstrated impressive antitumor effects, they have unique side effect profiles to be aware of as well.
The first ADC to be approved for metastatic triple-negative breast cancer is sacituzumab govitecan, a TROP-2-targeted agent that delivers a topoisomerase-1-directed cytotoxic payload to tumor cells. This drug was shown to significantly improve progression-free and overall survival compared to single-agent chemotherapy in the third-line setting and beyond in the ASCENT phase 3 clinical trial leading to its FDA approval in 2019.
While its antitumor effects are impressive, the off-target toxicity associated with this agent includes significant neutropenia, including febrile neutropenia, as well as GI toxicities such as diarrhea and nausea. Additionally, patients will likely experience full alopecia with this agent.
Use of white cell growth factors should be considered and may be useful in managing the hematologic toxicity associated with this agent. Moreover, patients should have antimotility agents on hand at home in case they experience diarrhea and should be in close communication with their physician or other providers. On occasion, consultation with a GI specialist is useful in cases of severe diarrhea.
At ASCO 2022, we are hearing more about this agent, sacituzumab govitecan, as phase 3 data will be presented relating to the use of this drug in hormone receptor-positive HER2-negative metastatic breast cancer.
Datopotamab deruxtecan, or Dato-DXd, has not yet been approved, but is demonstrating interesting antitumor benefits in a phase 1 clinical trial called TROPION-PanTumor01.
In addition to antitumor benefits, it is showing toxicity profiles that we need to be aware of including nausea. In addition, this agent has been associated with stomatitis and fatigue. Patients may experience cytopenias with this agent. So again, growth factors might be useful in helping to manage this particular side effect. More data is expected and eagerly anticipated to fully understand the safety profile of this agent in breast cancer.
So that's all the time we have for today. TROP-2-directed ADCs have hit the scene for treatment of triple-negative breast cancer. The efficacy data associated with sacituzumab govitecan is extremely exciting, but clinicians need to be informed about the potential toxicities associated with this agent in order to optimize outcomes for their patients.
In some cases, multidisciplinary management of adverse events is needed, most notably from our colleagues in gastroenterology.
Thank you so much for your attention. We hope this was 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.
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.
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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