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.
HER2-Directed ADCs in Breast Cancer
A Deep Dive into the Management of AEs Associated with ADCs
HER2-Directed ADCs in Lung Cancer
HER2-Directed ADCs in Lung Cancer
HER2-Directed ADCs in Lung Cancer
Welcome to CME on ReachMD. This episode is part of our MinuteCME curriculum and is titled “HER2-Directed ADCs in Lung 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. Justin Gainor, director of the Center for Thoracic Cancers at the Massachusetts General Hospital and an associate professor of medicine at Harvard Medical School.
Today, we'll be discussing HER2-directed antibody-drug conjugates [ADCs]. HER2 ADCs are really being explored in HER2-mutant non-small cell lung cancer. As a reminder, HER2 mutations are found in approximately 2% of patients with non-small cell lung cancer. These tend to occur in exon 20 and are most commonly insertion mutations. The reason why we think about HER2 ADCs in this patient population is that the presence of these mutations really leads to increased cycling of HER2 from the cell surface. And this is really something that can sensitize these tumors to antibody-drug conjugates.
Recently, we've seen exciting data with trastuzumab deruxtecan or T-DXd from the DESTINY-Lung01 study. In this study, we saw response rates of over 60% [54.9%] among patients with HER2-mutant non-small cell lung cancer. Given this promising activity, it's important to have a sense of what the safety profile of this agent is, particularly in non-small cell lung cancer. In general, about 50% of patients experienced a drug-related adverse event in the DESTINY-Lung study, the most common of which were nausea, fatigue, alopecia, and vomiting. I should add that, you know, a particularly important adverse event in this patient population was interstitial lung disease [ILD]. In DESTINY-Lung, 26% of patients had centrally adjudicated interstitial lung disease on this study. 75% of these events were grade 1 or grade 2, but 4 patients had grade 3 pulmonary events and 2 patients had grade 5 events; thus, prompt recognition of interstitial lung disease is critically important when using this agent.
So it's important to be able to recognize the adverse events associated with this agent, particularly as it has recently received breakthrough therapy designation by the United States FDA for treatment of EGFR-mutant non-small cell lung cancer.
When encountering interstitial lung disease in patients receiving T-DXd, generally, we want to be quite conservative. This agent currently is not FDA-approved in non-small cell lung cancer. It has breakthrough therapy designation, but I think we can take some of the lessons in areas where it is FDA-approved, such as in the setting of HER2-mutant breast cancer. When ILD is observed, according to the current FDA label, usually for grade 2 or higher ILD, we’re discontinuing therapy, and grade 2 implies patients are symptomatic. And so we should be coordinating with our pulmonary colleagues and considering initiation of corticosteroids to help manage the ILD.
Questions as we move to the future are what are the risk factors for ILD as well as whether the dose used in non-small cell lung cancer may be playing a role. The dose used in non-small cell lung cancer is higher than the FDA-approved dose of breast cancer. And so we really need additional data to explore that further.
T-DXd is not the only antibody-drug conjugate that's been explored in HER2-mutant non-small cell lung cancer. The earliest data that we saw was with T-DM1. And this was being explored in a phase 2 study led by investigators at Memorial Sloan Kettering, Bob Li and others. In that study, the most common adverse events that were drug related included elevated AST and ALT, thrombocytopenia, fatigue, infusion reactions, and nausea. Of course, when using any trastuzumab-based agent, we also have to be mindful of monitoring for cardiotoxicity and reductions in left ventricular ejection fraction. And so therefore, periodic echocardiograms are part of the ongoing management for these patients.
When encountering other adverse events such as cytopenias, generally, I would apply the same principles that I use towards chemotherapy-based side effects. That is, if I were seeing cytopenias, I would just dose interrupt and consider a dose reduction with subsequent cycles of therapy. Obviously, we want to discuss with our patients throughout to have a good understanding of what they're experiencing with respect to nausea, vomiting, and use standard antiemetics, just as we would with cytotoxic chemotherapy.
I think one misperception among clinicians is that with an antibody-drug conjugate, that we are eliminating some of the side effects that we see with traditional chemotherapies, be mindful that patients still can have nausea, vomiting, and using antiemetics as we normally would.
Ultimately, for both T-DXd and T-DM1, when you do encounter adverse events, particularly things like ILD as well as cardiotoxicity, it is critical to engage a multidisciplinary care team to help give patients the best management as well as to try to ensure that we're able to treat them with the most effective therapy. So I think we'll be seeing more of antibody-drug conjugates, particularly in the HER2 space based upon this success.
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).
Prova Education designs and executes continuing education founded on evidence-based medicine, clinical need, gap analysis, learner feedback, and more. Our mission is to serve as an inventive and relevant resource for clinical content and educational interventions across a broad spectrum of specialties.
Prova Education's methodology demonstrates a commitment to continuing medical education and the innovative assessment of its effects. Our goal is clear—to develop and deliver the very best education in the most impactful manner and to verify its results with progressive outcomes research.
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.
Reproduction of this material is not permitted without written permission from the copyright owner.
Our site requires a computer, tablet, or mobile device and a connection to the Internet. For best results, a high-speed Internet connection is recommended (DSL/Cable/Fibre). We also recommend using the latest version of your favorite browser to ensure compliance with W3C standards, such as Chrome, Safari, Firefox, or Microsoft Edge.