Abstract P2-08-12: Initial real world treatment patterns and outcomes of Abemaciclib for the treatment of HR+,HER2- metastatic breast cancer

Abstract

Background: Abemaciclib is a selective continually dosed cyclin-dependent kinase 4 and 6 (CDK 4&6) inhibitor approved as a single agent and in combination with endocrine therapy for the treatment of HR+,HER2- metastatic breast cancer (MBC). To date, few publications have reported the real world (rw) use of abemaciclib. This retrospective observational study aimed to describe baseline characteristics, treatment patterns, and outcomes among MBC patients treated with abemaciclib in the US. Methods: HR+,HER2- MBC patients who initiated treatment with abemaciclib on or after 6/30/2016 and at least 4 months prior to the data cutoff date (12/31/2018) were selected from the de-identified Flatiron Health electronic-health record-derived database for US patients. The data were predominantly from a community oncology setting. Baseline demographic and clinical characteristics were recorded at the start of abemaciclib therapy. Using technology-enabled abstraction, rw tumor response (rwTR) assessments on abemaciclib were collected to calculate rw best response (rwBR) which was defined as rw complete (rwCR) or partial response (rwPR). Time to first response (rwTTFR) was estimated using the Kaplan-Meier method. Descriptive statistics were used to summarize baseline characteristics and treatment patterns. Results: 118 female MBC patients were treated with abemaciclib. Baseline characteristics are shown in Table 1. Median age at abemaciclib initiation was 66.5 years (interquartile range [IQR] 57-73). 28.8% of patients received abemaciclib in first line (1L), 21.2% in second line (2L), 20.3% in third line (3L), and 29.7% in later lines (4+L). 12.7% of patients (n=15) received abemaciclib as a monotherapy, occurring mostly in later lines. Patients also received abemaciclib in combination with endocrine therapy, including fulvestrant (59.3%), or aromatase inhibitor (22.9%), or other treatment (5.1%). 24.6% of patients received prior treatment with a different CDK 4&6 inhibitor. Most patients (81.3%) had a starting dose of 150 mg of abemaciclib, while other starting doses included 200 mg (8.4%), 100 mg (4.2%), 50 mg (3.4%), or unknown dose (2.5%). During treatment, 6.8%, and 21.2% of patients had a dose reduction or schedule change, respectively. Of the patients with a schedule change (n=25), 72% changed from twice to once daily. Among all abemaciclib patients who had at least 1 rwTR assessment (n=68), 41.2% had a rwBR. Although not statistically significant, there was a trend toward higher rates of rwBR in 1L (65.0%) compared to 2L (37.4%), 3L (35.7%), and 4+L (22.3%). Median rwTTFR was 3.6 months (95% CI: 3.5-5.2). Conclusions: This is one of the first studies describing rw utilization of abemaciclib, and it provides initial insights into scheduling and dosing in an rw population. There is evidence of response to abemaciclib even in later lines. Future research will be needed as treatment patterns evolve and longer follow-up periods are available to further describe patient outcomes. Table 1: Baseline patient characteristicsAbemaciclibN = 118%Race:White63.6Non-white20.3Unknown/missing16.1Stage at initial diagnosis:I11.9II16.1III28.8IV34.7Not documented8.5Tumor grade at initial diagnosis:Grade 19.3Grade 245.8Grade 322.9Unknown/not documented22.0Time between initial and metastatic diagnosis dates among patients who were not metastatic at initial diagnosisa:< 2 years20.8≥ 2 years79.2Menopausal statusb:Post-menopausal93.2Pre-menopausal6.8Modified Charlson comorbidity index (CCI) statusc:0/Unknown72.0116.928.53+2.5Number of sites of metastases, median [IQR]d2.0 [1.0:3.0]Presence of lung metastases34.7Presence of liver metastases22.9Presence of brain metastases7.6Follow-up time (months), median [IQR]6.4 [4.1:9.5]a: Patients not metastatic at initial diagnosis (n=77)b: Derived using age and evidence of gonadotropin-releasing hormone agonistc: Excludes cancer diagnosisd: Interquartile Range (IQR) Citation Format: Gebra Cuyun Carter, Kristin M Sheffield, Anala Gossai, Yu-Jing Huang, Yajun Emily Zhu, Lee Bowman, Emily Nash Smith, Raina Mathur, Aaron B Cohen, Shrujal Baxi, Sarah Rybowski, Amy Lee Chong, Andrew D Seidman. Initial real world treatment patterns and outcomes of Abemaciclib for the treatment of HR+,HER2- metastatic breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-08-12.

CDK4/6 Inhibitors in HR+/HER2- Advanced/metastatic Breast Cancer: A Systematic Literature Review of Real-World Evidence Studies

“…For first-line ribociclib plus AI, dose reductions occurred in 55% of patients [49]. The lowest proportion of patients with dose reductions was reported for abemaciclib plus ET in all lines, ranging from 0 to 5.7% [48]. In all lines, the proportion of patients with dose reductions was 6.8% for abemaciclib alone or in combination with ET [48].…”

“…Median PFS was also reported as not reached in two studies (one study each for abemaciclib [48] and ribociclib [49]). Only one RWE study reported a median PFS for either of the other CDK4/6i: abemaciclib (monotherapy or plus ET) as second-or subsequent-line therapy was associated with a median PFS of 7 months [50].…”

“…Objective response rates (ORR) were reported in six studies (Supplementary Appendix 2) [37,39,41,45,48,55]. The lowest and highest ORR values were both reported for palbociclib plus AI across all lines of therapy, ranging from 5.6 to 79.5% (Table 2).…”

“…The percentage of patients who received a starting dose of palbociclib other than 125 mg/day ranged from 0.5 [56,57] to 40.7% [58] in these studies. One study each investigating ribociclib and abemaciclib reported the starting dose used: all patients in the ribociclib study received the recommended starting dose (600 mg/day) [59] and approximately 85% of patients in the abemaciclib study received the recommended starting dose (150 mg twice daily in combination with fulvestrant or an AI, 200 mg twice daily as monotherapy) [48].…”

CDK4/6 Inhibitor Treatments in Patients with Hormone Receptor Positive, Her2 Negative Advanced Breast Cancer: Potential Molecular Mechanisms, Clinical Implications and Future Perspectives

“…However, with a median PFS of 33.6 months rather than 22–28 months with palbociclib or with abemaciclib plus AI, and a relative risk reduction in death of 28% in the first-line setting of MONALEESA-3, ribociclib plus fulvestrant seems to be the preferred first-line treatment option in postmenopausal patients [ 19 ]. Moreover, whereas the data on OS for palbociclib and abemaciclib are still immature or are from real-world data of retrospective studies [ 29 , 30 ], the data on OS with ribociclib come directly from phase 3 trials [ 18 , 19 ].…”