Abstract P1-17-04: Hormone therapy (HT) brings more survival benefits than capecitabine (CAP) as maintenance therapy following the 1st-line chemotherapy in HR+/HER2-ABC/MBC: Update primary endpoint of OVERSTEP(ZJCHBC001)

Abstract Background: OVERSTEP is a multicenter, randomized clinical trial of capecitabine (CAP) versus endocrine therapy (HT) as maintenance therapy after 1st-line CAP-based combination chemotherapy in HR+/HER2- ABC/MBC. At 2020 SABCS conference, we have reported the primary endpoint (progression-free survival, PFS) of the OVERSTEP (NCT02597868) trial. With a median follow-up of 24.3 months,Median PFS (mPFS) of HT cohort was significantly longer than that of CAP group (17.5 months vs. 12.2 months, HR=0.625, 95%CI: 0.429-0.909, P=0.013). In this annual meeting, we will report the update of mPFS and the secondary endpoint (overall survival, OS). Methods: HR+ and HER2- metastatic breast cancer were enrolled in this study. All patients were histologically confirmed and received at least 4 cycles of CAP-based combination regimen as 1st-line salvage chemotherapy. The patients who achieved CR, PR or durable SD by RECIST criteria entered into the maintenance therapy setting (MT), and randomly (1:1 ratio) assigned to either CAP single or HT group. Randomization was done centrally with stratification by endocrine sensitive or resistance and visceral or non-visceral metastasis. The primary endpoint was mPFS, and the secondary endpoint was overall survival (OS), safety, et al. The superiority test was performed in all patients who received at least one dose maintenance therapy. The last follow-up ended in June 30, 2021. The medium follow-up duration was 41.4 months and the OS event was mature. Results: A total of 181 eligible patients were enrolled in this study from Jun 5, 2013 to Jan 14, 2019. After combined chemotherapy, 75.14% (n=136) cases entered into the maintenance therapy setting, and 24.86% case were disease progressed (PD) during combined chemotherapy. After a median follow-up of 41.4 months (IQR 21.57-79.23), the update mPFS in HT group remained superior to CAP cohort (17.7 months vs. 12.2 months, P=0.011). In addition, the median maintenance duration of HT group was significantly longer than that of CAP group (13.8 months vs. 7.4 months, P= 0.008). For endocrine sensitive patients, mPFS was greatly prolonged in HT group compared to CAP cohort (29.3 months vs. 14.8 months, HR=0.515, 95%CI: 0.269-0.988, P=0.042). Besides, in non-visceral metastasis patients, median PFS of HT group was 25.3 months which was longer than CAP subgroup 17.0 months (HR=0.54, 95%CI: 0.300-0.972, P=0.037). However, in endocrine resistance patients, there was no significant difference between HT and CAP group (13.6 months vs. 12.0 months, HR=0.791, 95%CI: 0.499-1.253, P=0.314). There was no difference observed between HT and CAP group in visceral involved cases (14.3 months vs. 11.0 months, HR= 0.668, 95%CI: 0.410-1.089, P=0.101). The median OS was 51.7 months (95%CI: 36.614-66.786) in HT cohort and 39.8 months (95%CI:14.083-65.517) in CAP group, respectively (HR=0.882, 95%CI: 0.550-1.414, P=0.600). Conclusions: For HR+ and HER2- MBC, after 1st-line salvage combined chemotherapy, HT maintenance therapy demonstrated sustained better survival benefits than CAP, especially for hormone sensitive or non-visceral involved patients. The primary endpoint of this study was successfully reached and the median OS was prolonged by 11.9-months. Citation Format: Xiao-Jia Wang, Jian Huang, Xi-ying Shao, Li Cai, Yong-mei Yin, Li-li Zhang, Peng Shen, Yan-xia Shi. Hormone therapy (HT) brings more survival benefits than capecitabine (CAP) as maintenance therapy following the 1st-line chemotherapy in HR+/HER2-ABC/MBC: Update primary endpoint of OVERSTEP(ZJCHBC001) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-17-04.