Sarat Chandarlapaty, MD, PhD
The invited discussant of TROPION-Breast01, Sarat Chandarlapaty, MD, PhD, Member of the Human Oncology and Pathogenesis Program at Memorial Sloan Kettering Cancer Center, New York, said the results suggest datopotamab deruxtecan (Dato-DXd) may be a good treatment option for a subset of patients, but many questions remain.
“The study asked which treatment is more effective for unselected patients with hormone receptor–positive, HER2-negative breast cancer previously treated with chemotherapy: a new chemotherapy regimen or Dato-DXd. With Dato-DXd, there was a clear improvement in progression-free survival (hazard ratio = 0.63). Although there was less toxicity overall (numerically fewer grade ≥ 3 toxicities), there was some increase in nausea and stomatitis, which could be clinically meaningful to patients,” he said.
More to Learn About Antibody-Drug Conjugates
So, Dr. Chandarlapaty said he would rather prescribe Dato-DXd but offered some caveats. “We have two antibody-drug conjugates approved in hormone receptor–positive breast cancer—sacituzumab govitecan-hziy and trastuzumab deruxtecan (T-DXd). Would I give Dato-DXd over one of these agents? I don’t have an answer for that,” he said.
Other questions remain: Can the antibody-drug conjugates (both with topoisomerase-targeting payloads) be given in sequence? Are these drugs preferable to inhibitors of the PI3K pathway?
“The elephant in the room is whether we are delivering on the full promise of antibody-drug conjugates,” stated Dr. Chandarlapaty. The clinical need is for highly selective and durably effective treatments, and to this end, there are many new antibody-drug conjugates in development that vary both in the antigens they target and in their payloads. Which patients will benefit from which drugs, and how they will compare with established standards, remains unknown.
“Clearly, Dato-DXd has benefit over later-line chemotherapy in hormone receptor–positive metastatic breast cancer, and it has a reasonable toxicity profile. The exact utility of it in comparison to some other newer regimens is uncertain. Translational research is urgently needed if we are to ultimately deliver on the promise of these agents in the clinic,” Dr. Chandarlapaty concluded.
DISCLOSURE: Dr. Chandarlapaty reported financial relationships with AstraZeneca, Boxer Capital, Nuvalent, SAGA Diagnostics, Neogenomics, Eli Lilly, Effector Tx, Genesis Tx, Prelude Tx, Casdin Capital, Blueprint, Novartis, Totus Med, and Odyssey Bio.
