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 Lung Cancer
A Deep Dive into the Management of AEs Associated with ADCs
TROP2-Directed ADCs in Lung Cancer
TROP2-Directed ADCs in Lung Cancer
TROP2-Directed ADCs in Lung Cancer
Welcome to CME on ReachMD. This episode is part of our MinuteCME curriculum and is titled “TROP2-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 for 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 TROP-2 antibody-drug conjugates. One of the major unmet needs in non-small cell lung cancer is to find effective therapies for patients after progression on platinum-doublet chemotherapy and immune checkpoint inhibitors, particularly among patients who do not have a targetable genetic alteration. Within these patients, what we've found is that non-small cell lung cancers commonly overexpress new targets such as TROP-2. And this could be an ideal target for an antibody-drug conjugate in these patients.
To date, we've seen data in non-small cell lung cancer with 2 different TROP-2 antibody-drug conjugates, the first being datopotamab deruxtecan or Dato-DXd. And this agent was being explored in the TROPION-PanTumor01 study. In this study, the antibody-drug conjugate was being explored in both dose-escalation as well as dose-expansion portions of this study.
Select treatment-emergent adverse events grade 3 or higher included things like decreased neutrophil count, which was found in about 1%. All grade was more on the order of 6%. Diarrhea was seen in approximately 6% of patients. Drug-related interstitial lung disease by independent adjudication was one of the noteworthy adverse events seen in 11% of patients on this study. Notably, at the highest dose level of 8 mg/kg, this was seen in 15% of patients. So that is one of the adverse events that clinicians should be mindful of, particularly in a non-small cell lung cancer patient population. Altogether, dose reductions occurred in 16% of patients, and dose interruptions occurred in approximately 18% of patients. In total, 15% of patients discontinued therapy due to treatment-emergent adverse events.
In parallel with the clinical development of Dato-DXd, we've seen data with sacituzumab govitecan. This is an agent that is now FDA-approved in the treatment of metastatic breast cancer and is now being explored in non-small cell lung cancer.
So far, it seems like TROP-2 expression by itself is not a biomarker of activity within non-small cell lung cancer. In preliminary studies using sacituzumab govitecan, grade 3 adverse events included neutropenia in about a quarter of patients, pneumonia in approximately 10% of patients, diarrhea in 7%, and nausea and fatigue in approximately 6% to 7%.
Adverse events appeared to be similar at the 2 dose levels that were explored, except for an increase in grade 3 or 4 neutropenia at the highest of the 2 doses tested. So this was 30% versus 13%. Ultimately, adverse events led to drug discontinuation in 2 patients. This was for grade 3 pneumonia and grade 3 recurrent pruritus.
Currently, we don't have any TROP-2 ADC that is FDA-approved in non-small cell lung cancer, though the data thus far has been quite encouraging, especially when put into the context of other disease settings such as the activity of sacituzumab govitecan in breast cancer. We're going to take some of the lessons from other disease areas as we start thinking about how to manage some of these adverse events. We'll also need to place this in the context of how we manage toxicity from cytotoxic chemotherapy such as dose interruptions, dose reductions, particularly around things like cytopenias. When we do see interstitial lung disease, having a low bar to interrupt therapy, reach out to our pulmonary colleagues, and introduce steroids if we do observe that, recognizing that non-small cell lung cancer patients may have multiple reasons to develop interstitial lung disease, so having a high level of suspicion for these patient populations.
As with other agents used in a non-small cell lung cancer patient population, employing a multidisciplinary approach will give our patients the best opportunity to have these adverse events managed most effectively.
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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.
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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 (email@example.com).
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This activity is supported by independent educational grants from AstraZeneca and Daiichi Sankyo.
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