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Abemaciclib effective for Ki67 reduction in certain postmenopausal women with breast cancer
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COPENHAGEN, Denmark — Neoadjuvant abemaciclib with or without anastrozole led to significantly greater reductions in tissue Ki67 after 2 weeks of treatment than anastrozole alone among postmenopausal women with hormone receptor–positive, HER-2–negative breast cancer, according to interim phase 2 study results presented at the European Society for Medical Oncology Congress.
“The change in proliferation gene mRNAs after 2 weeks of treatment, in blood or tumor, appeared to correlate with the change in Ki67, with a greater reduction in the abemaciclib-containing arms,” Sara Hurvitz, MD, director of the breast cancer program at UCLA Jonsson Comprehensive Cancer Center and co-director of the Santa Monica-UCLA Outpatient Oncology Practice, said during a presentation.
Abemaciclib (LY2835219, Eli Lilly) — an oral, small molecule inhibitor of CDK 4 and 6 — has shown single-agent antitumor activity in patients with refractory hormone receptor–positive metastatic breast cancer. The combination of abemaciclib and aromatase inhibitors has demonstrated an acceptable safety profile in this setting.
In the neoMONARCH study, Hurvitz and colleagues evaluated neoadjuvant abemaciclib in postmenopausal women with untreated, early-stage hormone receptor–positive, HER-2–negative breast cancer.
Researchers randomly assigned 173 women to neoadjuvant abemaciclib plus anastrozole (n = 56), abemaciclib monotherapy (n = 58) or anastrozole monotherapy (n = 59) for the first two weeks. At the conclusion of that regimen, all patients underwent a second core biopsy and then subsequently received the abemaciclib–anastrozole combination for 14 weeks.
Abemaciclib was administered in 150-mg oral doses every 12 hours, and anastrozole was administered in 1-mg oral doses daily. Patients also received loperamide as primary prophylaxis with each abemaciclib dose.
Changes in tissue Ki67 from baseline to week 2 served as the primary outcome measure. Additional study objectives included clinical, radiologic and pathological response; safety; and changes in proliferation-associated genes.
At a prespecified 9-month interim analysis, researchers had safety data for all 173 patients. They had Ki67 data for 64 patients and data related to proliferation-associated genes for 51 patients.
Researchers reported greater reduction in Ki67 geometric mean percent change from baseline among patients assigned the combination (-93.5%) and abemaciclib monotherapy (-93.1%) than those assigned anastrozole monotherapy (-71%; P < .001). The percentage of Ki67 responders — defined as patients with Ki67 levels below 2.7% at week 2 — was higher among those assigned the combination (69.6%) and abemaciclib monotherapy (68.4%) than anastrozole alone (22.7%).
Researchers identified no new safety concerns.
At the time of the 9-month analysis, no new safety signals were observed for abemaciclib and anastrozole in the study. The most frequently reported adverse event was any-grade diarrhea (45.7%, of which 2.9% was grade 3), followed by constipation (35.8%, of which 1.2% was grade 3).
"Further exploration of the predictive value of tumor mRNA in patients receiving abemaciclib is underway,” Hurvitz said. “neoMONARCH final results are expected to be presented at the end of this year.” – by Mark Leiser
For more information: Hurvitz S, et al. Abstract LBA13. Presented at: European Society for Medical Oncology Congress; Oct. 7-11, 2016; Copenhagen, Denmark.
Disclosure: The researchers report funding from Eli Lilly. Hurvitz reports relationships with Amgen, Bayer, Biomarin, Boehringer Ingelheim, Dignitana, Eli Lilly, Genentech, GlaxoSmithKline, Medivation, Merrimack, Novartis, OBI Pharma, Puma Biotechnology, Pfizer and Roche. Please see the abstract for a list of all other researchers’ relevant financial disclosures.