Formal discussant Daniel G. Stover, MD, of The Ohio State University Comprehensive Cancer Center, said the SONIA and PALMIRA trials raised several questions. Can CDK4/6 inhibitors be personalized and differentiated? Can patients delay treatment with these agents? Should all patients receive a CDK4/6 inhibitor as part of first-line therapy? Can a subset of patients be treated with endocrine therapy alone? Are all CDK4/6 inhibitors identical?

Daniel G. Stover, MD

“Initially, we thought these agents were interchangeable, but subsequent evidence from other clinical trials with different designs suggests they may not be,” stated Dr. Stover. “However, as yet, we do not have head-to-head studies that can guide therapy selection for our patients.”

Another point made by Dr. Stover is that fulvestrant may not be the optimal second-line therapy. “A growing menu of molecularly directed or nonmolecularly directed second-line therapies are becoming available. It’s unclear whether fulvestrant, which was appropriate at the time the study was designed, would still hold up with other therapies in play,” he noted.

“We have a limited signal [from these trials] as to which patients can delay CDK4/6 inhibitor therapy. One of the exciting things to think about is identifying who may be the very good–risk patients who can delay treatment with a CDK4/6 inhibitor. For most patients, endocrine therapy plus a CDK4/6 inhibitor is still the appropriate treatment. However, I would argue that we need additional biomarkers [for patient selection], be it RNA-based biomarkers, novel PET imaging, or perhaps circulating tumor DNA dynamics,” Dr. Stover commented. 

DISCLOSURE: Dr. Stover has received research funding from Novartis and NeoGenomics Laboratories.