Prognostic characteristics in hormone receptor-positive advanced breast cancer and characterization of abemaciclib efficacy

Abstract

CDK4 & 6 inhibitors have enhanced the effectiveness of endocrine therapy (ET) in patients with advanced breast cancer (ABC). This paper presents exploratory analyses examining patient and disease characteristics that may inform in whom and when abemaciclib should be initiated. MONARCH 2 and 3 enrolled women with HR+, HER2- ABC. In MONARCH 2, patients whose disease had progressed while receiving ET were administered fulvestrant+abemaciclib/placebo. In MONARCH 3, patients received a nonsteroidal aromatase inhibitor+abemaciclib/placebo as initial therapy for advanced disease. A combined analysis of the two studies was performed to determine significant prognostic factors. Efficacy results (PFS and ORR in patients with measurable disease) were examined for patient subgroups corresponding to each significant prognostic factor. Analysis of clinical factors confirmed the following to have prognostic value: bone-only disease, liver metastases, tumor grade, progesterone receptor status, performance status, treatment-free interval (TFI) from the end of adjuvant ET, and time from diagnosis to recurrence. Prognosis was poorer in patients with liver metastases, progesterone receptor-negative tumors, high grade tumors, or short TFI (<36 months). Benefit (PFS hazard ratio, ORR increase) from abemaciclib was observed in all patient subgroups. Patients with indicators of poor prognosis had the largest benefit from the addition of abemaciclib. However, in MONARCH 3, for patients with certain good prognostic factors (TFI ≥ 36 months, bone-only disease) ET achieved a median PFS of >20 months. These analyses identified prognostic factors and demonstrated that patients with poor prognostic factors derived the largest benefit from the addition of abemaciclib.

Ki67 and PR in Patients Treated with CDK4/6 Inhibitors: A Real-World Experience

“…Di Leo et al performed an interesting exploratory analysis, examining patient and disease characteristics to identify the patients most likely to benefit from abemaciclib and the best time to initiate treatment [ 24 ]. The analysis of clinical factors showed that bone-only disease, liver metastases, tumor grade, PR expression, performance status, treatment-free interval from the end of adjuvant endocrine therapy, and time from diagnosis to recurrence had a prognostic value.…”

“…The analysis of clinical factors showed that bone-only disease, liver metastases, tumor grade, PR expression, performance status, treatment-free interval from the end of adjuvant endocrine therapy, and time from diagnosis to recurrence had a prognostic value. Patients with poor prognostic factors showed the greatest benefit from the addition of abemaciclib [ 24 ].…”

Real-world patient-reported outcomes of women receiving initial endocrine-based therapy for HR+/HER2− advanced breast cancer in five European countries

“…However, the presence of liver metastases (in 18% of EU5 women providing PRO data) was not an independent predictor of HRQoL in our regression analysis. Analyses of phase III studies aimed at identifying which subgroup of patients may benefit most from a combination of ET plus CDK4 & 6 inhibitor as initial therapy for advanced disease found that patients with indicators of a poor prognosis (liver metastases, progesterone receptor-negative tumors, high-grade tumors, or treatment-free interval < 36 months) benefited most from this combination therapy [ 49 ]. Thus, greater use of ET plus a CDK4 & 6 inhibitor as initial therapy for advanced disease in women with HR+/HER2− advanced breast cancer may have the potential to maintain/improve patient HRQoL.…”

Abemaciclib as an original inhibitor of cyclin-dependent kinase for the treatment of luminal HER2-negative disseminated breast cancer

“…1 и 2); в то же время при наличии определенных факторов благоприятного прогноза, таких как интервал без лечения после окончания ЭТ ≥ 36 мес., метастазирование только в кости, на одной только ЭТ медиана ВБП превышала 20 мес. [70]. Таким образом, комбинация абемациклиба с ЭТ по сравнению с одной только ЭТ значимо повышает эффективность лечения пациентов с неблагоприятным течением заболевания и высоким риском быстрого прогрессирования болезни как в 1-й, так и во 2-й линиях лечения.…”