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Expert Point of View: Seth Wander, MD, PhD


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Seth Wander, MD, PhD

Seth Wander, MD, PhD

Seth Wander, MD, PhD, Assistant Professor, Mass General Cancer Center, Boston, commented on the findings of the EMERALD trial.

“We have seen a large amount of new data emerging related to elacestrant and other novel SERDs [selective estrogen receptor degraders]. Despite initial expectations based on preclinical and early-phase studies, with more phase II and III data, we are starting to see some differences among these agents. How much of these differences are due to the drug itself, the clinical trial design, or the patient population will take time to unravel,” he said.

“Resistance to CDK4/6 [cyclin-dependent kinases 4 and 6] inhibitors is the result of a variety of diverse genomic and molecular mechanisms. The new data related to elascestrant presented at SABCS are interesting and may show a subset of patients who develop later, acquired resistance to CDK4/6 inhibitors and may be more endocrine-sensitive. These data are still evolving, but support the notion that a particular subgroup of patients are poised to derive more clinical benefit from strategies focused upon endocrine signaling in the second- or third-line setting. We now have positive data related to elacestrant’s use in hormone-refractory breast cancer, and it will likely find a place in clinical practice,” Dr. Wander commented.

“Unanswered questions remain focused upon who might be the best patient for these novel SERDs: all patients, or those with ESR1-mutated tumors? Are there specific clinical features that help us identify these groups? Are there other genomic or molecular features of the tumor that can help us guide therapy? These data add to this important conversation and suggest that the duration on prior CDK4/6 therapy might be a tool we can use to select patients for this drug,” he stated. 

DISCLOSURE: Dr. Wander has served as an advisor or consultant to Biovica, Eli Lilly, Foundation Medicine, Hologic, Pfizer, and Veracyte; and has received institutional research support from Eli Lilly, Genentech, Nuvation Bio, and Regor Therapeutics.


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Elacestrant—an investigational oral selective estrogen receptor degrader (SERD)—achieved longer progression-free survival vs standard-of-care endocrine monotherapy as second- or third-line therapy in patients with estrogen receptor–positive, HER2-negative advanced or metastatic breast cancer in the ...

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