Dr Rimm on Factors That Influence Treatment Sequencing With ADCs in Breast Cancer

“In some settings, and [maybe] more settings in the future, there will be more than 1 ADC available to the patient and the oncologist, [and we are going to] have to choose which one to use first.”

David Rimm, MD, PhD, the Anthony N. Brady Professor of Pathology and a professor of medicine (medical oncology) at the Yale School of Medicine; as well as director of the Tissue Microarray Facility, director of Yale Pathology Tissue Services, and director of the Physician Scientist Training Program at Yale Cancer Center, discussed the precision measurement and strategic sequencing of antibody-drug conjugates (ADCs) in patients with breast cancer, beginning with the assertion that these treatments should be fundamentally classified as targeted therapies. Rimm noted that his laboratory has focused its efforts over the last several years on the precise measurement of therapeutic targets. This task, he explained, is a core function of the pathologist, who is responsible for judging, reading, and scoring the target to provide a clinical score. Rimm’s lab has worked on quantifying these targets using a highly specific concentration unit: attomoles per square millimeter.

The objective of this research is to demonstrate the clinical importance of these assays in the oncology landscape, Rimm continued. He argued that measuring the target is vital for predicting how a patient will respond to a particular treatment and for determining which ADC is most appropriate for a given patient. This becomes relevant in future clinical scenarios where multiple ADCs may be available to a patient, requiring oncologists to make strategic choices regarding which agent to use first, according to Rimm.

Although traditional chemotherapy remains a component of treatment, Rimm observed that the optimal sequencing of these therapies in later-line metastatic settings is currently a subject of debate. He noted that there is currently no consensus on the matter; some oncologists prefer to use ADCs in a specific order, whereas others suggest splicing traditional chemotherapy between the administration of 2 different ADCs. At this point, Rimm pointed out, there is little evidence to support one sequencing method over another.

However, Rimm highlighted that as clinical trial data mature, more definitive evidence will emerge for the field. He identified the phase 2 TRADE-DXd trial (NCT06533826) as a key study to watch. As results from this trial mature, Rimm said he expects to see developing evidence regarding the most effective order for drug administration and whether chemotherapy should be integrated into the sequence of ADCs.