The leading laboratory abnormalities of grade 3 or 4 were a reduction in white blood cell count (27.7%) and a reduction in neutrophil count (26.9%).
The rate of serious adverse events was 24.2%. Three patients died while on therapy or within a month of stopping.
Overall, 49.2% of patients needed a dose reduction, most commonly because of diarrhea, prompting a session attendee to ask whether perhaps a lower starting dose of abemaciclib “would be better tolerated and just as effective.”
The dose used in MONARCH 1 was the maximal tolerated dose established by the phase I trial, Dr. Dickler replied. “Diarrhea obviously was common, but 50% of patients did not require a dose reduction. And when diarrhea did develop, it was really manageable.”
“So I think as a single agent, it’s not unreasonable to start at 200 mg twice daily. In combination with endocrine therapy, in the studies MONARCH 2 and 3, the concurrent dose is 150 mg twice daily,” she pointed out.
The investigators are currently analyzing biomarkers in tumor tissue and plasma to ascertain any predictors of response, according to Dr. Dickler.
Patients with brain metastases were excluded from the trial, she noted. However, “abemaciclib appears to cross the blood-brain barrier, so there is a lot of interest in looking at abemaciclib in patients with brain metastases, and there is a trial that’s ongoing specifically for that.”
Dr. Dickler disclosed that she has a consulting or advisory role with AstraZeneca, Bristol-Myers Squibb, Eisai, Genentech/Roche, Merrimack, Novartis, Pfizer, and Syndax, and that she receives research funding (institutional) from Genentech/Roche, Lilly, and Novartis. The trial was sponsored by Eli Lilly and Company.