Are CDK4/6i costs and side effects worth it?
The findings challenge the need for using CDK4/6 inhibitors as first-line treatment in this population, according to Dr. Sonke, who also raised the following related questions.
“If you were a patient, would you consider a treatment that offers no improvement in quality of life and does not improve overall survival? As a doctor or nurse, would you recommend such a treatment to your patient that nearly doubles the incidence of side effects? And if you were responsible for covering the costs of this treatment, whether as an individual or health care insurance, would you consider it worth $200,000?”
For many patients, particularly in the first line setting where resistance mechanisms are less prevalent, endocrine therapy alone remains an excellent option,” said Dr. Sonke during his presentation.
During the discussion portion of the session, Daniel Stover, MD, who is an associate professor of translational therapeutics at Ohio State University Comprehensive Cancer Center, Columbus, pointed out that the lack of differences in the subanalyses leaves little guidance for physicians.
“We really have a limited signal on who can delay CDK4/6 inhibitors. I think one of the most important outcomes of this study is the focus on the patient, as there were substantially fewer adverse events and of course we need to think about financial toxicity as well,” he said. “I think one of the things that is perhaps most exciting to think about is who are the very good risk patients who can delay CDK4/6 inhibitor [therapy]? I think for the majority of patients, endocrine therapy plus CDK4/6 inhibitor is still the appropriate treatment, but I would argue we need additional biomarkers, be it RNA-based biomarkers, novel PET imaging, or perhaps [circulating tumor] DNA dynamics.”
Do cost savings and reduced side effects outweigh first-line PFS benefit?
During the question-and-answer session, William Sikov, MD, spoke up from the audience in support of Dr. Sonke’s conclusions.
“Clearly there are still patients who benefit from that approach, but I think that we have reached an inflection point: I posit that the question has now changed. [We should not ask] why a certain patient should not receive a CDK4/6 inhibitor, but why a certain patient should receive a CDK4/6 inhibitor in the first-line setting,” said Dr. Sikov, who is professor of medicine at Brown University, Providence, R.I.
Dr. Sonke agreed that first-line CDK4/6i is appropriate for some patients, and later echoed the need for biomarkers, but he said that researchers have so far had little luck in identifying any.
“Of course, it’s a shared decision-making between the patient and a doctor, but I think the baseline would be for all of us to consider first line single-agent endocrine therapy,” he said.
Session comoderator Michael Danso, MD, praised the trial but questioned whether the strategy would be adopted in places like the United States, where cost savings is not a major emphasis.
“Progression-free survival is so significant in the first line setting that I can’t imagine that many oncologists in the U.S. will adopt this approach. The other thing is that this was [almost] all palbociclib, so the question remains, would having a different cyclin dependent kinase inhibitor result in the same results? I think the jury’s still out,” said Dr. Danso, who is the research director at Virginia Oncology Associates, Norfolk.
The study was funded by the Dutch government and Dutch Health Insurers. Dr. Sonke has consulted for or advised Biovica, Novartis, and Seagen. He has received research support through his institution from Agendia, AstraZeneca/Merck, Merck Sharp & Dohme, Novartis, Roche, and Seagen. Dr. Sikov has been a speaker for Lilly. Dr. Danso has received honoraria from Amgen and has consulted or advised Immunomedics, Novartis, Pfizer, and Seagen.
