Hope S. Rugo, MD
The combination of abemaciclib (Verzenio) and pembrolizumab (Keytruda) showed preliminary signs of activity without additive toxicity for patients with pretreated HR-positive, HER2-negative metastatic breast cancer, according to early results from a pilot trial presented in a poster at the 2017 San Antonio Breast Cancer Symposium (SABCS).1
In the JPCE trial, the partial response (PR) rate at 16 weeks was 14.3% and it was 6.8% in the MONARCH-1 trial. There were no complete responses in either trial. The rate of stable disease was similar between both trials at 60.7% in JPCE and 60.6% in MONARCH-1. Fewer patients had developed progressive disease in the JPCE trial (17.9% and 25.0%). In JPCE, the disease control rate (DCR) was 75% and in MONARCH-1 it was 67.4% at the early assessment.
The combination of pembrolizumab and abemaciclib did not demonstrate any unexpected adverse events (AEs), with the most common treatment-emergent AE being diarrhea (78.6%), which is a known toxicity associated with abemaciclib. Most of these events were grade 1 or 2 in severity and 7.1% of patients had grade 3 diarrhea. Serious AEs were experienced by 21.4% of patients and AEs led to discontinuation for 14.3% of those treated with the combination. There were no grade 4 or 5 AEs.
Outside of diarrhea, the most common treatment-emergent AEs of clinical interest were pruritus (25%), rash (10.7%), renal failure (7.1%), dermatitis acneiform (7.1%), and colitis, hypothyroidism, hyperthyroidism, pneumonitis (3.6% each). Grade 3 neutropenia occurred in 28.6% of patients treated with the combination.
"We're continuing our follow-up, with our real hallmark follow-up being at 24 weeks. Obviously, we need to follow these patients out until they are also a year after the last patient was enrolled, in order to really make a post-hoc comparison with the MONARCH-1 data," she said. "We're also evaluating PD-L1 status, which I think is going to be really important, as well as tumor infiltrating lymphocytes and tumor samples, which we required for all patients."
The data cutoff for the SABCS presentation was June 2017, and examined data after a minimum of 16 weeks of follow-up. With this timeframe, 12 months of follow-up for the trial should be available for analysis in the first quarter of 2018.
- Rugo HS, Kabos P, Dickler MN, et al. A phase 1b study of abemaciclib plus pembrolizumab for patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (MBC). Presented at: 2017 San Antonio Breast Cancer Symposium; San Antonio, Texas, December 5-9, 2017. Presentation P1-09-01.
- Dickler MN, Tolaney S, Rugo HS, et al. MONARCH 1, a phase 2 study of abemaciclib, a CDK4 and CDK6 inhibitor, as a single agent, in patients with refractory HR+/HER2- metastatic breast cancer. Clin Cancer Res. 2017;23(17):5218-5224.
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