Real-world treatment patterns and outcomes in patients with HR+/HER2- metastatic breast cancer treated with chemotherapy in the United States

Abstract

Background: Until recently, treatment options for patients with hormone receptor-positive/human epidermal growth factor 2-negative (HR+/HER2-) metastatic breast cancer (mBC) and resistance to endocrine therapy were limited to chemotherapy. This real-world study describes treatment patterns and outcomes in patients treated with chemotherapy in the United States before approval of antibody-drug conjugates.

Patients and methods: This retrospective, observational study included adults with HR+/HER2- mBC from the ConcertAI Patient360™ Breast Cancer dataset who initiated their first chemotherapy in the metastatic setting between January 2011 and June 2021. Treatment patterns were described; real-world overall survival, time to next treatment or death, and real-world progression-free survival were evaluated for all eligible patients and patients treated with subsequent chemotherapy. Index dates were the start date of each chemotherapy treatment.

Results: Among 1545 eligible patients, 76% were white, 12% had Eastern Cooperative Oncology Group performance status ≥2, 38% had de novo mBC, and median age was 61 years (range, 52-69 years). Within the index period, capecitabine was used the most as the first chemotherapy agent and decreased in later treatments, while the use of eribulin increased between first and fourth chemotherapies. Median (95% confidence interval) real-world overall survival was 23.3 months (21.3-25.4 months) from start of first chemotherapy, time to next treatment or death was 6.5 months (5.9-7.1 months), and real-world progression-free survival was 6.9 months (6.4-7.6 months); median times from second, third, and fourth chemotherapies decreased with each additional chemotherapy treatment.

Conclusions: This real-world study demonstrates that for patients with HR+/HER2- mBC, chemotherapy provides relatively limited survival benefit which decreases with each additional chemotherapy line, and highlights the need for improved treatment options.

Keywords: HER2-negative; RWE; antibody–drug conjugates; chemotherapy; hormone receptor-positive; metastatic breast cancer.

Figure 1

(A) Patient selection and (B) disposition. BC, breast cancer; CT, chemotherapy; ER+, estrogen receptor-positive; HER2−, human epidermal growth factor receptor 2-negative; HR+, hormone receptor-positive; mBC, metastatic BC; PR+, progesterone receptor-positive. ^aPatients were excluded if they did not receive next CT, or if they received next CT but it started after the end of the patient identification period, after censoring due to a change in follow-up biomarker status, or on the last activity date.

Figure 2

Treatment patterns by line of metastatic treatment for patients in the primary cohort. ET-based regimen included ET monotherapy (aromatase inhibitor, fulvestrant, and SERM), ET + CDK4/6i, ET + other TT [ET combined with mTORi, PI3Ki, poly(ADP-ribose) polymerase inhibitor, or tyrosine kinase inhibitor], and ET + other [ET + ET combination therapy and ET + other combination therapy not included in ET + CDK4/6i, ET + other TT, and ET + CT (± other)]; ET + CT (± other) included ET combined with CT with or without targeted therapy; CT included CT monotherapy and CT combination therapy (defined as any combination of at least 2 CT and CT + TT); other included ADCs/investigational treatments, palbociclib, abemaciclib, olaparib, alpelisib, everolimus, and other monotherapy/combination therapy. ADC, antibody–drug conjugate; ADP, adenosine diphosphate; CDK4/6i, cyclin-dependent kinase 4/6 inhibitor; CT, chemotherapy; ET, endocrine therapy; L, line of treatment; mTORi, mammalian target of rapamycin inhibitor; PI3Ki, phosphoinositide 3-kinase inhibitor; SERM, selective estrogen receptor modulator; TT, targeted therapy.

Figure 3

Single-agent chemotherapy use across the first four chemotherapy treatments received by patients in the primary cohort. Other includes epirubicin and investigational agents, paclitaxel includes paclitaxel and albumin-bound paclitaxel. Percentages are based on the total number of patients in each CT treatment group. CT, chemotherapy.

Figure 4

Kaplan–Meier curves for (A) rwOS, (B) TTNTD, and (C) rwPFS in the primary cohort. CT, chemotherapy; rwOS, real-world overall survival; rwPFS, real-world progression-free survival; TTNTD, time to next treatment or death.