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.
Nectin-4-Directed ADCs in Bladder Cancer
Nectin-4-Directed ADCs in Bladder Cancer
Welcome to CME on ReachMD. This episode is part of our MinuteCME curriculum and is titled “Nectin-4-Directed ADCs in Bladder Cancer”.
Prior to beginning the activity, please be sure to review the faculty and commercial support disclosure statements as well as the learning objectives.
Antibody-drug conjugates, or ADCs, have been around for over 20 years. However, the first ADC wasn't approved in bladder cancer until just a few years ago. With ADCs finally in the treatment algorithm, patients have experienced significantly improved overall survival. But while the novel mechanism of ADCs allows for cytotoxic agents to be delivered to the cancer cells and limits the overabundance of toxicities, there are still adverse events that we care providers need to know how to manage. So let's dive right in.
This is CME on ReachMD, and I'm Dr. Gopa Iyer.
Enfortumab vedotin, or EV, is an ADC that binds to nectin-4, a protein expressed on the surface of most bladder cancers, and delivers an MMAE [monomethyl auristatin E] cytotoxic payload. Common adverse events related to EV include peripheral neuropathy, skin rash, ocular disorders, and hyperglycemia. Most patients receiving EV experience peripheral neuropathy related to the MMAE payload. Sensory neuropathy is more common than motor neuropathy and frequently presents as numbness in the fingers and toes.
Strategies for managing neuropathy include dose interruptions and/or dose reductions, as well as discontinuation of therapy in order to prevent permanent side effects. And the specific intervention should be based on CTCAE [Common Terminology Criteria for Adverse Events] grading criteria. Early recognition of peripheral neuropathy is critical to prevent worsening of side effects, and patients should be advised to report any symptoms promptly.
The most common skin-related symptoms associated with EV are maculopapular rash, pruritus, changes in skin pigmentation, and dry skin. While most skin changes are mild and resolve with topical therapies, up to 13% of patients have experienced grade 3 skin reactions, and severe and fatal cutaneous adverse reactions such as Stevens-Johnson Syndrome have been reported.
A multidisciplinary approach is essential to successful management of rash, including referral to a dermatologist whenever possible. Patients should report any cutaneous symptoms promptly. Use of sunscreen and moisturizers can be quite effective for mild symptoms such as pruritus and dry skin, while topical steroid creams are useful in managing rash.
Ocular toxicities that have been reported with EV most commonly include dry eyes and blurry vision. While a baseline eye exam is not required with EV, patients who have known ocular conditions may benefit from ophthalmologic monitoring while on treatment.
Hyperglycemia is another side effect observed in approximately 11% of patients on clinical trials of EV, with some patients experiencing diabetic ketoacidosis and even death. The incidence was higher in patients with preexisting hyperglycemia, such as from diabetes, and in patients with a higher body mass index and an elevated hemoglobin A1c. Patients with a baseline hemoglobin A1c greater than or equal to 8% were excluded from the clinical trials of EV. Blood glucose levels should be monitored while on EV, and EV should be held for blood glucose levels greater than or equal to 250 mg/dL.
Unfortunately, that's all the time we have today. So I want to leave you with this final take-home message. Both EV and SG [sacituzumab govitecan] have specific side effect profiles that are related in part to the different cytotoxic payloads of these compounds. It is essential for care providers to familiarize themselves with these toxicities and monitor for them routinely in patients who receive these drugs. Most of the side effects of EV can be managed successfully if caught early and treated immediately. And a multidisciplinary approach is highly recommended for the management of these toxicities.
Thank you for your attention and have a wonderful day.
You have been listening to CME on ReachMD. This activity is provided by Prova Education and is part of our MinuteCME curriculum.
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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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