Dr Moore on AEs Associated With ADC Treatment in Gynecologic Cancers

“We are still learning how to predict and mitigate [ADC-related toxicities] earlier so that we don’t have deaths. All of these drugs have unfortunately been compromised by deaths, mainly due to ILD, which is the toxicity that we worry most about with ADCs.”

Kathleen N. Moore, MD, MS, professor, Section of Gynecologic Oncology, associate director, Clinical Research, Stephenson Cancer Center, director, Oklahoma TSET Phase I Program, University of Oklahoma College of Medicine, The University of Oklahoma Health Sciences, discusses adverse effects (AEs) associated with the use of antibody-drug conjugates (ADCs) for the treatment of patients with gynecologic cancers.

ADCs are associated with complex toxicity profiles, primarily due to the linker technologies and conjugated toxins used in their design, Moore begins. Although target-specific toxicities occur, much of the AEs stem from how the payloads interact with cells and circulate in the body, she reports, saying that understanding these mechanisms is key to predicting and managing these AEs.

ADCs exhibit on-target, off-tumor effects, as well as off-target, off-tumor toxicities, which contribute to their unique safety concerns, Moore continues. Interstitial lung disease (ILD) is among the most concerning toxicities, she explains. Although this AE can sometimes lead to fatalities, improvements in recognition and management strategies have reduced such outcomes, Moore emphasizes. ILD often goes unrecognized due to the difficulty of interpreting subtle inflammatory changes on CT scans, especially in patients with pre-existing abnormalities, according to Moore. Historically, waxing and waning ground-glass opacities were often dismissed as benign findings, she says. However, education and awareness efforts have emphasized the importance of monitoring these findings, even in asymptomatic patients, to prevent treatment-related complications, she reiterates.

Despite progress in identifying and mitigating ILD, 2 scenarios continue to pose risks, she notes. For example, in some cases, unrecognized early ILD leads to progressive and fatal outcomes, she references. In others, certain patients experience rapid-onset respiratory distress that defies rescue efforts, she notes. Ongoing research into biomarkers aims to identify patients at higher risk for developing severe ILD, she explains. Surveillance protocols and intervention strategies, detailed in recent publications, play an essential role in mitigating these risks and improving patient outcomes, Moore concludes.