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November 20, 2020 - Patients from Asian countries with hormone receptor–positive, HER2-negative breast cancer may have a higher risk of disease recurrence than those from non-Asian countries, suggesting that this population may benefit from additional adjuvant treatment with abemaciclib.
Patients from Asian countries with hormone receptor (HR)–positive, HER2-negative breast cancer may have a higher risk of disease recurrence than those from non-Asian countries, suggesting that this population may benefit from additional adjuvant treatment with abemaciclib (Verzenio), according to additional data from the phase 3 monarchE trial that were presented during the ESMO Asia Virtual Congress 2020.1
Results from the analysis of baseline characteristics of patients from Asia who were enrolled on the trial showed that this population of patients were younger than those from non-Asian countries, they were more commonly premenopausal, and they had a higher incidence of 4 or more positive nodes.
“These characteristics suggest that patients with HR-positive, HER2-negative early breast cancer from Asian countries may have a higher risk of recurrence than patients from non-Asian countries and would benefit from additional adjuvant treatment beyond the current standard of care,” In Hae Park, MD, of the Center for Breast Cancer of the National Cancer Center in Korea, said during an oral presentation on the data.
Approximately 20% of patients with HR-positive, HER2-negative early breast cancer will experience disease recurrence within the first 10 years of diagnosis. It has been demonstrated that specific high-risk clinical or pathological features could potentially increase risk of recurrence.
The open-label, phase 3 monarchE trial enrolled 5637 patients with HR-positive, HER2-negative, high-risk early breast cancer. To be eligible for enrollment, patients had to have 4 or more positive axillary lymph nodes (ALN) or 1 to 3 ALN and a tumor that was 5 cm or larger, grade 3 disease, or a centrally tested Ki67 of 20% or higher.
In the trial, participants were randomized 1:1 to receive either abemaciclib at a twice daily dose of 150 mg for up to 2 years in combination with endocrine therapy for 5 to 10 years as clinically indicated or endocrine therapy alone for the same duration. A total of 1155 patients were randomized from Asian countries, including China, Japan, Korea, Taiwan, Singapore, and Hong Kong. Stratification factors included prior chemotherapy (yes vs no), menopausal status (pre vs post), and region (North America/Europe vs Asia vs other).
The primary end point of the trial was invasive disease-free survival (iDFS) per STEEP criteria, while key secondary end points comprised distant relapse-free survival (DRFS), overall survival, safety, patient-reported outcomes, and pharmacokinetics.
Results from monarchE presented during the 2020 ESMO Virtual Congress demonstrated that the addition of abemaciclib to endocrine therapy resulted in a significant 25.3% reduction in the risk of invasive disease compared with endocrine therapy alone in this patient population (HR, 0.747; 95% CI, 0.598-0.932; 2-sided P = .0096).2 Moreover, the iDFS rate at 2 years was 92.2% in the abemaciclib arm versus 88.7% in the endocrine-alone arm; this translated to an absolute improvement of 3.5%.
The addition of abemaciclib to standard-of-care endocrine treatment also significantly impacted DRFS across all prespecified subgroups analyzed, with patients in the investigational arm experiencing a 28.3% reduction in the risk of distant recurrence (HR, 0.717; 95% CI, 0.559-0.920; P = .0085). At 2 years, the DRFS rate was 93.6% in the abemaciclib arm versus 90.3% in the endocrine-alone arm, which translated to an absolute improvement of 3.3%. Ninety-two patients in the investigational arm experienced distant recurrence versus 142 patients in the endocrine-alone arm.
In the analysis presented during the ESMO Asia Virtual Congress 2020, Park shared data on the differences in patient demographics between patients from Asian countries versus those from non-Asian countries. Moreover, patients from Asian countries were observed to be younger than those from non-Asian countries, with a median age of 48 years versus 52 years, respectively. Additionally, more patients from Asian countries were found to be premenopausal at the time of diagnosis compared with patients from non-Asian countries, at approximately 59% versus approximately 40%.
“Fifty-five percent of patients received prior chemotherapy, indicating the high-risk nature of this study population,” noted Park.
When examining high-risk disease characteristics, approximately 65% of patients from Asian countries had 4 or more positive ALN compared with approximately 58% of those from non-Asian countries. With regard to histological grade, pathologic tumor size, central Ki-67 index, and progesterone receptor status, characteristics were observed to be similar between the 2 groups.
Approximately 34% of patients from Asian countries had 1 to 3 positive nodes versus about 41% of those from non-Asian countries. In the former group, 6.5% had tumors that were 5 cm or greater upon pathology, 4.9% had tumors that were 5 cm or greater upon imaging, 18.4% had histologic grade 3 disease, and 8.8% had central Ki-67 of 20% or greater. In the latter group, these rates were 9.2%, 5.7%, 23.1%, and 7.9%, respectively.
Additionally, 39.9% of patients from Asian countries received tamoxifen as their first on-study endocrine therapy versus 29.2% of those from non-Asian countries; 12.5% and 6.4% of patients, respectively, also received ovarian suppression. No patients from non-Asian countries received toremifene versus 1.45% of those from Asian countries.
Moreover, 58.7% of patients from Asian countries received aromatase inhibitors compared with 70.8% of patients from non-Asian countries. Letrozole was the most commonly used agent in both groups, at 33.6% versus 39.5%, respectively. Other agents included anastrozole (15.0% vs 23.8%, respectively) and exemestane (10.2% vs 7.6%).
“As expected, we saw an increased incidence of premenopausal patients [from Asian countries] so we also saw an increase in the proportion of patients who received ovarian suppression in combination with endocrine therapy,” added Park. In those who received aromatase inhibitors, 22.5% of patients from Asian countries also received ovarian suppression versus 12.2% of those from non-Asian countries.
Lastly, fewer patients from Asian countries received concomitant therapy with bone-modifying agents versus those from non-Asian countries, at 9.0% versus 16.4%, respectively.
“To our knowledge, these are the first reported baseline characteristics data in patients from Asian countries with HR-positive, HER2-negative, node-positive, high-risk early breast cancer in a CDK4/6 inhibitor trial,” Park concluded.
1. Jiang Z, Nakayama T, Nakamura S, et al. Baseline characteristics of patients from Asia enrolled in monarchE, evaluating abemaciclib in high risk early breast cancer. Presented at: ESMO Asia Virtual Congress 2020; November 20-22, 2020; Virtual. Abstract LBA1.
2. Johnston SRD, Harbeck N, Hegg R, et al. Abemaciclib combined with endocrine therapy for the adjuvant treatment of HR+, HER2-, node-positive, high risk, early breast cancer (monarchE). Ann Oncol. 2020;31(suppl 4):1143-1144. doi:10.1016/j.annonc.2020.08.2238