In the first 11 months following the FDA approval of the CDK4/6 inhibitor abemaciclib as a single agent and in combination with endocrine therapy for the treatment of hormone receptor-positive, HER2-negative metastatic breast cancer, it is being used heterogeneously, including in patients with characteristics indicative of worse prognosis.
Gebra Cuyun Carter, PhD
In the first 11 months following the FDA approval of the CDK4/6 inhibitor abemaciclib (Verzenio) as a single agent and in combination with endocrine therapy for the treatment of hormone receptor (HR)-positive, HER2-negative metastatic breast cancer, it is being used heterogeneously, including in patients with characteristics indicative of worse prognosis.
In a retrospective observational study, real-world use of abemaciclib has resulted in a 12-month real-world progression-free survival (rwPFS) rate of 61.7%, and the median rwPFS has not been reached (95% CI, 9.02-NR), reported Gebra Cuyun Carter, PhD, at the 2019 San Antonio Breast Cancer Symposium.
The Flatiron Health electronic health record-derived database was used to identify 118 female patients with HR-positive, HER2-negative metastatic breast cancer who initiated treatment with abemaciclib between June 30, 2016 and August 31, 2018, and at least 4 months prior to the cutoff date of December 31, 2018. The median follow-up time for this analysis was 6.4 months. Almost all (98.3%) patients were treated in a community oncology setting.
“It’s important to understand how abemaciclib is being used because you want to understand if it’s similar to its indication,” said Carter, research scientist at Eli Lilly and Company, Indianapolis. “Clinical trial patients are often a homogeneous patient population…only 3% of cancer patients participate in clinical trials…it’s important to understand utilization in a more heterogeneous patient population in a clinical practice setting. You’re looking at patients who are often excluded or choose not to participate in clinical trials or don’t have the option to participate.”
“The follow-up time is 6 months, so it’s early utilization with limited follow-up time,” she said. “So we were limited in some of the outcomes we could assess. We did look at real-world tumor response, which is one that we felt was more robust at the time.”
Real-world best response in all abemaciclib recipients who had at least 1 real-world response assessment was 41.2% (n = 28 of 68), including a partial response (PR) in 35.3%, stable disease (SD) in 33.8%, and complete response (CR) in 5.9%. One-fourth of patients (25%) had progressive disease.
Response rates declined with use of abemaciclib in each subsequent line, but even in the fourth or later line, the response rate was 22.3% (n = 4 of 18) , with 1 (5.6%) CR and 3 (16.7%) PRs. Eight (44.4%) patients had SD as their best response to fourth or later line abemaciclib. The real-world time to first response across all abemaciclib-containing regimens was 3.6 months.
Abemaciclib was used in the first-line setting in 34 of the 118 (28.8%) abemaciclib recipients, in the second line in 25 (21.2%), in the third line in 24 (20.3%), and in the fourth or later line in 35 (29.7%).
As part of a combination, abemaciclib was most often used with fulvestrant (n = 70), followed by an aromatase inhibitor (AI; n = 27), and the combination of fulvestrant and an AI (n = 6).
In the first line, abemaciclib was most often used with fulvestrant (n = 18) or an AI (11), and was used as monotherapy in the first line in 2 patients. In the 25 patients in whom abemaciclib was used in the second-line setting, use in combination with fulvestrant was the most common use (n = 18). Abemaciclib was not used as monotherapy in the second line. In the third line, abemaciclib was again used most often with fulvestrant (n = 17). When used in the fourth line or later, abemaciclib was used most often with fulvestrant (n = 17), followed by abemaciclib monotherapy (n = 12).
About one-fourth (24.6%) of the 118 abemaciclib recipients received prior treatment with a CDK4/6 inhibitor (palbociclib [Ibrance] or ribociclib [Kisqali]).
According to stage at initial diagnosis, abemaciclib was used most often in patients with stage IV (34.7%) and stage III (28.8%) metastatic breast cancer. Stage was not documented in 8.5%.
According to tumor grade at initial diagnosis, abemaciclib was used most often in patients with tumor grade 2 (45.8%) followed by grade 3 (22.9%), and grade 1 (9.3%). Tumor stage was unknown or undocumented in 22.0% of abemaciclib recipients.
Some 86.4% of abemaciclib recipients were progesterone receptor—positive. The time between initial diagnosis and diagnosis of metastasis among the patients who were not metastatic at initial diagnosis was ≥2 years in 79.2% of abemaciclib-treated patients and ≤2 years in 20.8%. The median number of sites of metastases was 2.0. About half (49.2%) had visceral metastases, and sites of metastases were lung in 34.7%, liver in 22.9%, bone in 82.2%, distant lymph nodes in 30.5%, brain in 7.6%, and central nervous system in 3.4%.
About 85% of patients initiated abemaciclib at a starting dosage that is consistent with FDA-approved labeling. Most patients appeared to tolerate treatment: dose reduction was not required in 93.2%, 62.7% did not have a dose held, and 78.8% of patients did not have a change in dosing schedule.
“Some of our follow-up steps are to get a more robust sample size so that we can explore some of these regimen-specific cohorts in the future,” said Carter.
Carter GC, Sheffield KM, Gossan A, et al. Initial real world treatment patterns and outcomes of Abemaciclib for the treatment of HR+,HER2- metastatic breast cancer. Presented at: 2019 San Antonio Breast Cancer Symposium; December 10-14, 2019; San Antonio, TX. Abstract P2-08-12.