Background:

Treatment guidelines for hormone receptor-positive/human epidermal growth factor receptor-2-negative (HR+/HER2-) metastatic breast cancer (mBC) recommend extending the time on treatment (TOT) of endocrine therapy (ET) prior to the initiation of chemotherapy (CT) to avoid its serious side effects and preserve patients' quality of life. Everolimus-based therapy (EVE), fulvestrant monotherapy (FUL mono), and capecitabine monotherapy (CAP mono) are among the latest ET and CT agents approved for the treatment of HR+/HER2- mBC in the US. This retrospective claims analysis compared TOT among HR+/HER2- mBC patients who received EVE versus those who received FUL mono or CAP mono respectively.

Methods:

Postmenopausal women with HR+/HER2- mBC who initiated ≥ 1 new line of therapy for mBC between 7/20/2012 (the approval date of EVE, the latest of all three therapies) and 3/31/2014 (which allowed for ≥ 3 months of potential follow-up) after a non-steroidal aromatase inhibitor were identified from the MarketScan and PharMetrics databases (2002Q1-2014Q2) using an algorithm adapted from the literature. Treatment discontinuation was defined as a treatment gap of ≥ 60 days. Patients' lines of therapies were classified into mutually-exclusive regimen groups (i.e., EVE, FUL mono, and CAP mono) and followed until discontinuation of the line of therapy, end of insurance eligibility, or data cut-off (06/30/2014). Patients who did not discontinue their treatment were censored at the end of follow-up. TOT was compared between EVE versus FUL mono and versus CAP mono using Kaplan-Meier (K-M) analyses with log-rank tests and multivariable Cox models adjusting for the line of therapy and differences in patient characteristics, including age, insurance type, de novo vs non-de-novo mBC, prior use of CT for mBC, sites of metastases (e.g., bone, brain, and visceral), and Charlson comorbidity index.

Results:

Across the first four lines of therapies for mBC, a total of 940 EVE, 953 FUL mono, and 721 CAP mono regimens were included. Based on the different lines of therapies, the K-M estimators of median TOT ranged from 5.5 to 7.2 months for EVE, 4.9 to 8.4 months for FUL mono, and 3.5 to 6.0 months for CAP mono.

Table 1. Comparison of TOT between EVE, FUL mono, and CAP mono by line of therapy

 Median TOT (months)
 EVEFUL monoCAP mono
Line 16.2 8.4 3.5* 
Line 26.2 5.6 4.6* 
Line 37.2 5.3* 6.0* 
Line 45.5 4.9 5.1* 
 Median TOT (months)
 EVEFUL monoCAP mono
Line 16.2 8.4 3.5* 
Line 26.2 5.6 4.6* 
Line 37.2 5.3* 6.0* 
Line 45.5 4.9 5.1* 

*indicates p-value <0.05 for pairwise log-rank tests in comparison with EVE.

Pooling all lines of therapies, EVE was associated with significantly longer TOT compared to FUL mono (multivariable-adjusted hazard ratio [HR] = 0.87, 95% confidence interval [CI]: 0.76-0.99) or CAP mono (multivariable-adjusted HR = 0.73, 95% CI: 0.64-0.83). Similar results were observed in each line of therapy.

Conclusions:

This real-world US claims study of postmenopausal women with HR+/HER2- mBC showed that patients receiving EVE experienced significantly longer TOT than those receiving FUL mono or CAP mono, suggesting a comparative advantage of EVE in extending the duration of ET.

Citation Format: Li N, Hao Y, Kageleiry A, Peeples M, Fang A, Koo V, Guérin A. Time on treatment of everolimus, fulvestrant, and capecitabine for the treatment of HR+/HER2- metastatic breast cancer: A retrospective claims study in the US. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P4-13-14.