CDK4/6 inhibitor abemaciclib plus endocrine therapy led to significant benefits in a population of predominantly Chinese women with advanced hormone receptor–positive/HER2-negative breast cancer, according to data from 2 randomized trials presented at the 2019 ESMO Congress.
Zefei Jiang, MD
Data from 2 randomized trials showed that the CDK4/6 inhibitor abemaciclib (Verzenio) and endocrine therapy showed significant benefit in Chinese women with advanced hormone receptor-positive/HER2-negative (HR+/HER-) breast cancer.
In a study of women with newly diagnosed advanced disease or relapse beyond 1 year after treatment, those randomized to abemaciclib and a nonsteroidal aromatase inhibitor (NSAI) had yet to reach a median progression-free survival (PFS), although the lower confidence interval exceeded 22 months. In contrast, women who received endocrine therapy and placebo had a median PFS of 14.73 months.
A study of patients with early relapse yielded a median PFS of 11.47 months with abemaciclib and fulvestrant, as compared with 5.59 months for women who received fulvestrant and placebo.
The results were consistent with and extended findings from prior global trials of abemaciclib and endocrine therapy, investigators reported at 2019 ESMO Congress.
“Abemaciclib plus a nonsteroidal aromatase inhibitor or fulvestrant showed statistically significant and clinically meaningful improvement in progression-free survival and objective response rate in predominately Chinese patients with HR-positive/HER2-negative advanced breast cancer,” Zefei Jiang, MD, of the Fifth Medical Center of Chinese PLA General Hospital in Beijing. “The benefit from abemaciclib was overall consistent across subgroups.
“The safety profile of abemaciclib in combination with nonsteroidal aromatase inhibitors or fulvestrant was tolerable in this patient population, and no new safety signals were observed.”
The results of the 2 trials not only were consistent with the global trials but also with each other, said invited discussant Miguel Martin, MD, PhD, of the Gregorio Maranon University General Hospital in Madrid.
“The abemaciclib arm performed significantly better in both trials,” said Martin.
Outcomes in the fulvestrant component of the Chinese study were inferior to those of the global registration trials for abemaciclib, which Martin attributed to a higher risk patient population (endocrine-resistant disease). Nonetheless, differences between the abemaciclib and placebo groups were similar in magnitude to the differences observed in the registration trials, he added.
The trial, known as MONARCH Plus, was a continuation of the MONARCH clinical development program that led to regulatory approval of abemaciclib. MONARCH Plus enrolled patients from nations that did not participate in the global trials: Brazil, India, and South Africa, in addition to China.
Investigators conducted two separate randomized trials evaluating the addition of abemaciclib to endocrine therapy for advanced HR+/HER- breast cancer. One trial included 463 women with no prior systemic therapy for advanced/metastatic disease and no prior endocrine therapy or relapse >1 year after completion of endocrine therapy with an agent other than anastrozole (Arimidex) or letrozole (Femara) or de novo metastatic breast cancer. The patients were randomized 2:1 to abemaciclib plus an NSAI (anastrozole or letrozole) or to placebo and an NSAI.
The second trial included 157 women whose disease relapsed during or within 1 year of initial endocrine treatment with an NSAI. They were randomized 2:1 to fulvestrant plus abemaciclib or placebo.
The primary outcome was investigator-assessed PFS in the cohort of patients with newly diagnosed disease. The key secondary outcome was investigator-assessed PFS in the patients with relapsed/recurrent disease.
In both studies, the baseline characteristics were well balanced between the abemaciclib and placebo groups.
The primary analysis showed that abemaciclib plus an NSAI reduced the hazard for disease progression or death by 50% (P= .0001). Subgroup analysis favored abemaciclib for almost all patients. Notable exceptions were patients with de novo metastatic disease, patients aged ≥65 years, and patients enrolled in countries other than China.
Abemaciclib also conferred a significant advantage for objective response in patients with measurable disease (65.9% vs 36.1%;P<.0001) and those without (56.0% vs 30.3%; P <.0001). Similar differences were observed for disease control rate and clinical benefit rate.
Analysis of the secondary endpoint showed that abemaciclib plus fulvestrant reduced the hazard for disease progression or death by 62% versus placebo (P<.0001). The advantage persisted across all subgroups evaluated, Jiang and colleagues reported. Objective response rate, disease control rate, and clinical benefit rate were improved with the addition of abemaciclib to fulvestrant.
In both studies, adverse events occurred more often in patients treated with abemaciclib compared with placebo. However, the overall safety profile was consistent with the known adverse events associated with the CDK4/6 inhibitor.
Jiang Z, Hu X, Zhang Q, et al. MONARCHplus: A phase III trial of abemaciclib plus nonsteroidal aromatase inhibitor (NSAI) or fulvestrant (F) for women with HR+/HER2- advanced breast cancer (ABC). Presented at ESMO 2019; September 27-October 1, 2019; Barcelona, Spain. Abstract LBA25.