On October 6, 2017 Eli Lilly and Company (NYSE: LLY) reported that interim results from the double-blind, placebo-controlled Phase 3 MONARCH 3 study evaluating VerzenioTM (abemaciclib), a cyclin-dependent kinase (CDK)4 & 6 inhibitor, in combination with a nonsteroidal aromatase inhibitor (NSAI) (anastrozole or letrozole) were published online in the Journal of Clinical Oncology (JCO) (Press release, Eli Lilly, OCT 6, 2017, View Source [SID1234520807]). These data, presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2017 Congress in September, demonstrated that abemaciclib plus an NSAI resulted in a statistically significant improvement in progression-free survival (PFS) and objective response rate (ORR) compared to an NSAI alone in women with hormone-receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer.

“The significant results seen in MONARCH 3 confirm the clinical value of combining abemaciclib with an aromatase inhibitor in patients with endocrine-sensitive advanced breast cancer, and we look forward to seeing the final PFS data in the coming months,” said lead author Matthew P. Goetz, M.D., professor of oncology and pharmacology at Mayo Clinic and co-lead investigator of the MONARCH 3 study. “These data further demonstrate that abemaciclib is an effective treatment in the CDK4 & 6 class. This class represents a new standard of care in the treatment of advanced breast cancer.”

MONARCH 3 met a rigorous threshold for demonstrating efficacy at the time of pre-planned interim analysis with a 46 percent reduction in the risk of progression or death in patients receiving initial therapy for metastatic disease. The median PFS for abemaciclib in combination with an NSAI was not reached (i.e., the disease had not progressed significantly), compared to 14.7 months in the placebo arm (HR: 0.54; 95% CI: 0.41-0.72; P=0.000021). These results are supported by an improvement in response rate, with a 59.2 percent ORR in patients with measurable disease, including five patients (1.5%) achieving a complete response. Median duration of response (DoR) was not reached in the abemaciclib-plus-NSAI arm. Final PFS results are expected at the end of the year and will be presented at a scientific congress in the first half of 2018.

“At Lilly, we remain deeply committed to delivering standard-of-care changing medicines that improve the lives of many cancer patients,” said Levi Garraway, M.D., Ph.D., senior vice president, global development and medical affairs, Lilly Oncology. “We now have evidence from two randomized trials showing that the addition of Verzenio to an endocrine therapy provides clinical benefit to women with metastatic breast cancer and we look forward to further advancing our MONARCH clinical program.”

In MONARCH 3, abemaciclib in combination with an NSAI was generally well tolerated. The most frequent adverse events (AEs) of any grade in the abemaciclib-plus-NSAI arm were diarrhea, neutropenia, fatigue, infections, and nausea. Of these, the reported Grade 3/4 AEs in the abemaciclib-plus-NSAI arm versus the placebo-plus-NSAI arm were diarrhea (Grade 3: 9.5% vs 1.2%; no Grade 4 observed), neutropenia (Grade 3: 19.6% vs 0.6%; Grade 4: 1.5% vs 0.6%), fatigue (Grade 3: 1.8% vs 0%; no Grade 4 observed), infections (Grade 3: 4.0% vs 2.5%; Grade 4: 0.9% vs 0.6%), and nausea (Grade 3: 0.9% vs 1.2%; no Grade 4 observed).

Severity and frequency of diarrhea generally decreased following 28 days (one month), and was managed with over-the-counter antidiarrheal medication and dose adjustment. The majority (76.3%) of patients in the abemaciclib-plus-NSAI arm with an AE of diarrhea did not require treatment modification (dose interruption, reduction, or discontinuation), and 2.3 percent of patients discontinued treatment with abemaciclib due to diarrhea.

The MONARCH 3 study also included exploratory subgroup analyses that underscored consistency of results (when compared to the overall intention-to-treat [ITT] results) in patients with certain challenging disease characteristics. Further studies are needed to explore these findings.

MONARCH 3 was designed to evaluate the efficacy and safety of abemaciclib in combination with NSAIs as initial endocrine-based therapy for postmenopausal women with advanced (locoregionally recurrent or metastatic) breast cancer who have had no prior systemic treatment for advanced disease. If neoadjuvant/adjuvant endocrine therapy was administered, a disease-free interval of more than 12 months since completion of endocrine therapy was required. A total of 493 patients were randomized 2:1 to receive 150 mg of abemaciclib or placebo orally twice a day, without interruption, given in combination with either 1 mg of anastrozole or 2.5 mg of letrozole once daily until disease progression or unacceptable toxicity. The primary endpoint of the study was PFS, with key secondary endpoints of ORR, DoR, overall survival and safety.