A presentation at the 2018 American Society of Clinical Oncology Annual Meeting in early June built on positive results witnessed in earlier trials of abemaciclib, and demonstrated that selective cyclin-dependent kinase 4 and 6 (CDK 4/6) inhibitor continues to benefit patients even after disease progression.
The MONARCH 2 trial showed that abemaciclib combined with fulvestrant significantly improved both progression free survival and objective response rates compared to fulvestrant alone in women with hormone receptor positive and human epidermal growth factor receptor 2 negative advanced breast cancer who had progressed while or within 12 months of receiving (neo)adjuvant endocrine therapy. The MONARCH 3 clinical trial demonstrated that abemaciclib combined with a nonsteroidal aromatase inhibitor extended median progression free survival and improved objective response rate compared to monotherapy with a nonsteroidal aromatase inhibitor in postmenopausal women with hormone receptor positive and human epidermal growth factor receptor 2 negative advanced breast cancer as an initial therapy.
Lead mammography technician. (Source: 10th Air Force)
The latest study analyzed results from both phase 3 trials to determine whether abemaciclib impacted subsequent treatment and specifically analyzed time to subsequent chemotherapy and time to second disease progression. Together, the trials enrolled 1,162 women. For the current analysis, the researchers calculated time to subsequent chemotherapy from the date of randomization. The researchers calculated time to second disease progression from randomization to the earlier of the date of discontinuation of the first line of post-discontinuation therapy or the starting date of the second line of post-discontinuation therapy.
About half of the participants in the trials received a post-discontinuation systemic therapy, according to the study. Among MONARCH 2 patients, 35% received chemotherapy, 28% endocrine therapy, 18% a targeted agent and 6% another therapy. Among MONARCH 3 patients, 26% received chemotherapy, 38% received endocrine therapy, 15% a targeted agent and 7% another therapy.
The researchers found that patients who received abemaciclib with fulvestrant had a longer period before initiation of chemotherapy, 26.33 months for those who received just fulvestrant and median not yet reached for the abemaciclib arm. As of the date of data closure, that represented a reduction in risk of starting subsequent chemotherapy of at least 35%. Patients who received abemaciclib with an aromatase inhibitor in the first-line setting saw at least a 46% reduction in risk of initiating subsequent chemotherapy. Women who received monotherapy with aromatase inhibitor had a median time to subsequent chemotherapy of 33.52 months, while the median had not been reached for those who received the abemaciclib combination, according to the study.
Similarly, abemaciclib extended the time to second disease progression, with a 22% reduction in risk in the abemaciclib/fulvestrant group and a 26% risk reduction among those who received abemaciclib with an aromatase inhibitor.Overall, the treatment benefit of abemaciclib [and fulvestrant] or [and non-steroidal aromatase inhibitor] was extended to the next line of the therapy after the initial disease progression,” the researchers concluded.