Maura Dickler, MD
As a single agent, abemaciclib has shown exciting potential in heavily pretreated patients with refractory, hormone-receptor (HR)–positive, HER2-negative advanced breast cancer, following phase II findings of the MONARCH 1 trial.
Results of the single-arm study, which were presented during the 2016 ASCO Annual Meeting1
, show that the CDK4/6 inhibitor induced a response rate of nearly 20% in this patient population. The median progression-free survival (PFS) was 6 months (95% CI 4.2-7.5) and the median overall survival (OS) was 17.7 months (95% CI, 16 to not reached). Previously, abemaciclib received a breakthrough therapy designation in this setting from the FDA in October 2015.
"The MONARCH 1 study was really a proof-of-concept trial, so it's a relatively small phase II study looking at a cell-cycle inhibitor as a single-agent," explains lead investigator Maura Dickler, MD. "At least to date, this is the first cell-cycle inhibitor that has single-agent activity. So that was really the intent of the trial, to confirm the activity that was seen in the phase I trial. I think doctors in the community should look for the results of MONARCH 2 and MONARCH 3, which should be coming soon."
Objective response rate (ORR) was the primary outcome measure. Secondary endpoints included duration of response, PFS, OS, clinical benefit rate, and safety. The investigator-assessed, confirmed ORR was 19.7% (n = 26; 95% CI, 13.3-27.5), which included all partial responses (PR). The rate of patients with stable disease (SD) ≥6 months was 22.7%, leading to a clinical benefit rate (complete response + PR + SD ≥6 months) of 42.4%. The median time to response was 3.7 months and the median duration of response was 8.6 months. Thirty-four patients had progressive disease.
The MONARCH 1 trial included 132 patients with HR+/HER2- metastatic breast cancer who progressed during or after endocrine therapy and chemotherapy. Additionally, patients had received a median of 3 (range, 1-8) prior lines of therapy—including a median of 2 lines of chemotherapy—for metastatic disease. Sixty-seven patients (50.8%) had received fulvestrant in the metastatic setting. With chemotherapy, 68.9% (n = 91) of patients had received a taxane and 55.3 % (n = 73) of patients had received capecitabine in the metastatic setting.
In an interview with OncLive
, Dickler, medical oncologist, Memorial Sloan Kettering Cancer Center, discusses findings from the recent phase II study exploring abemaciclib as a single agent in patients with HR-positive breast cancer, along with an upcoming phase III trial looking at combination strategies. Dickler also discusses the PI3K-alpha inhibitor taselisib, which was examined in combination with fulvestrant in a phase II study.
OncLive: Can you tell us about the MONARCH1 trial?
: MONARCH 1 was a straight phase II study of single-agent abemaciclib, a CDK4 and CDK6 inhibitor, in previously treated women with hormone receptor (HR)-positive metastatic breast cancer. It was a multicenter trial. The study enrolled 132 women who had previously received endocrine therapy and also at least one, but not more than two, chemotherapies for metastatic disease. It was a group of women where we typically wouldn't offer additional endocrine therapy, and that their typical next treatment would be chemotherapy. We know in that setting, response rates for chemotherapy are in the order of 10% to 20% with progression-free survival (PFS) of about 3 to 4 months.
This trial was specifically testing single-agent abemaciclib in a more heavily-pretreated patient population, and I mention that because it's different from the other abemaciclib studies that are ongoing, which are actually earlier in metastatic disease, either in first-line endocrine therapy with the aromatase inhibitors, or in combination with second-line endocrine therapy like fulvestrant.