Abemaciclib stabilizes brain metastases in breast cancer subtype
CHICAGO — Abemaciclib resulted in a clinically meaningful effect on intracranial response rate in patients with brain metastases secondary to hormone receptor-positive, HER2-negative metastatic breast cancer, according to a study presented at the ASCO Annual Meeting.
Brain metastases develop in about 30% to 50% of patients with metastatic breast cancer; however, there are only a few treatment options available, according to Sara M. Tolaney, MD, MPH, breast medical oncologist at Dana-Farber Cancer Institute, who served as an investigator on the study.
Such metastases are “a challenging clinical scenario,” Carey K. Anders, MD, a medical oncologist at Duke Cancer Center who was also involved in the study, told HemOnc Today.
“Despite local therapy approaches, such as radiation or surgery, progression of brain metastases results in neurologic symptoms that can impair patients’ quality of life,” Anders continued. “CDK4/6 inhibitors have revolutionized the way we treat HR-positive metastatic breast cancer.”
Abemaciclib (Verzenio, Eli Lilly) is a CDK4/6 inhibitor with blood brain barrier permeability, Tolaney told HemOnc Today. Their study aimed to evaluate the activity of abemaciclib in patients with new or progressive HR-positive, HER2-negative brain metastases.
Anders and colleagues analyzed data from the JPBO study, focusing on the cohort of patients with brain metastases secondary to HR-positive, HER2-negative metastatic breast cancer (n = 58).
All patients eligible for inclusion in the analysis (n = 52) had at least one brain metastasis that was either new or had not been irradiated previously and measured 10 mm or greater. Patients being treated with endocrine therapy at the time of enrollment were allowed to continue the therapy if extracranial disease was stable for 3 or more months and progression of the central nervous system occurred while receiving endocrine therapy.
Participants received 200 mg abemaciclib orally twice a day.
The primary endpoint was objective intracranial response rate [OIRR; (CR+PR)]) based on Neuro-Oncology brain metastases response assessment criteria (RANO-BM) criteria, according to the researchers. Other endpoints included intracranial clinical benefit rate, defined as CR plus PR plus SD persisting for 6 or more months, PFS and safety.
Patients had been treated with a median of 4 prior systemic therapies. In the metastatic setting, 75% of participants had been treated previously with chemotherapies (range, 0-6; median, 2) and 71% had received endocrine therapy (range, o to 4; median, 1).
Prior to the study, whole brain radiotherapy was conducted in 50% of patients; stereotactic radiosurgery was conducted in 39% and surgical resection of brain metastases was conducted in 8%. There was a median of 9.4 months from the time of radiation to study enrollment.
The researchers identified 3 patients with a confirmed intracranial response (OIRR, 6%) .
“While the intracranial ORR of abemaciclib at 6% did not meet our prespecified response rate of 11%, the intracranial clinical benefit rate was approximately 25%,” Anders said. “These patients had stabilization of their brain metastases for 6 months or greater.”
A reduction in the sum of intracranial target lesions was observed in 38% of patients. Participants demonstrated a median PFS of 4.4 months (95% CI, 2.6-5.5). No new safety or tolerability concerns for abemaciclib were identified.
“These results are meaningful findings in a population that often has poor prognosis and a limited number of treatment options,” Tolaney told HemOnc Today.
This research demonstrates that abemaciclib as a single agent stabilizes HR-positive breast cancer brain metastases, which is extremely similar to data on lapatinib (Tykerb, Novartis) for HER2-positive breast cancer brain metastases, Anders added.
“The next step will be to examine novel combination therapies with abemaciclib to augment response rates for our patients with metastatic, HR-positive breast cancer and brain metastases,” she said. – by Alaina Tedesco
Anders CK, et al. Abstract 1017. Presented at: ASCO Annual Meeting; May 31-June 4, 2019; Chicago.
Disclosures: Anders reports no relevant financial disclosures. Tolaney reports consulting or advising for, research funding from or travel, accommodations or expenses from AstraZeneca, Bristol-Myers Squibb, Celldex, Cyclacel, Eisai, Eli Lilly and Company, Exelixis, Genentech, Genentech/Roche, Immunomedics, Merck, NanoString Technologies, Nektar, Novartis, Pfizer, Puma Biotechnology, Sanofi and Tesaro. Please see the abstract for a list of all other authors’ relevant financial disclosures.