Safety results
“In terms of safety, the rate of grade 3 or higher treatment-related AEs in the Dato-DXd arm was less as compared to investigator choice of chemotherapy. This is a bit different from most of the studies; in general we see that the rate of adverse events is higher in the intervention arm as compared to the control arm,” Dr. Bardia commented.
Rates of dose reductions and dose interruptions due to treatment-related AEs were also lower with the ADC.
There were no patient deaths associated with Dato-DXd. One patient assigned to chemotherapy died from a complication associated with febrile neutropenia.
Most treatment-related AEs occurring in 15% of patients and AEs of special interest were of grade 1 and manageable.
The most common toxicities seen with the ADC were oral mucositis and dry eye. The most common side effects with chemotherapy were neutropenia and anemia, “the usual side effects you would expect with chemotherapy,” Dr. Bardia said, pointing out that the rate of grade 3 neutropenia was 31% with standard chemotherapy, compared with 1% with Dato-DXd.
Good, but we can do better
ESMO invited discussant Sarat Chandarlapaty, MD, PhD, a breast oncologist at Memorial Sloan Kettering Cancer Center in New York, commented that while the trial data showed superior efficacy and safety with Dato-DXd, compared with standard chemotherapy, it’s still unclear how it and other ADCs on the market and in the research pipeline may be used in therapy for this patient population.
“Would I rather prescribe Dato-DXd or more chemo after 1 to 2 lines of chemo in unselected HR-positive, HER2-negative breast cancer? The answer is Dato-DXd, but it leaves several unanswered questions for us,” he said.
“First, we have two ADCs approved in HR-positive breast cancer: another TROP2 ADC sacituzumab [govitecan] and a HER2 ADC trastuzumab deruxtecan. Would I rather give Dato over one of these? I don’t have an answer,” he added.
In addition, it’s unknown whether these drugs, which have the same topoisomerase-targeted payload, could be given in sequence, and there are as yet no clear answers as to whether patients might do better with Dato-DXd or with a PIK3ca inhibitor.
“I would say that the elephant in the room is really another question, and that is, ‘Is Dato-DXd in this context delivering on the promise of an ADC?’ ” Dr. Chandarlapaty said.
“I think translational research is urgently needed if we’re ultimately to deliver on the promise of these agents in the clinic,” he concluded.
The TROPION-Breast01 study is sponsored AstraZeneca, which is collaborating with Daiichi-Sankyo on global development and commercialization of Dato-DXd. Dr. Bardia disclosed advisory board activities and institutional research funding from AstraZeneca and Daiichi-Sankyo and others. Dr. Chandarlapaty disclosed research funding from both companies, and advisory board activities for AstraZeneca and others.