Hormone therapy (HT) or capecitabine (CAP) as maintenance therapy following the first-line chemotherapy in HR+/HER2-ABC/MBC: Secondary endpoint adverse effects (AEs) and toxicity report of OVERSTEP Trial (ZJCH15001/CBCSG 035).

1068 Background: OVERSTEP (NCT02597868) 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 reported the primary endpoint (progression-free survival, PFS) at follow-up of 24.3 months, at 2021 SABCS, repoted the PFS and OS at follow-up of 41.4 months. Here, we reported the secondary endpoint Adverse effects (AEs). Methods: Total of 181 patients with HR+ and HER2- MBC were enrolled in this study from Jun, 2013 to Jan, 2019. All the patients 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. 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), we reported the secondary endpoint Adverse effects (AEs). Results: In PPS, hematologic toxicities in ET group and CT group were as follows, anemia (69.6% vs 64.2%), leukopenia (60.8% vs 50.8%), neutropenia (66.7% vs 31.2%), thrombocytopenia (26.1% vs 26.9%). The non-hematologic toxicities were hand-foot syndrome (HFS) (33.3 vs 41.8%), increased ALT (50.7 % vs 37.3%), increased AST (53.6% vs 37.3%), hyperbilirubinemia (32.2% vs 25.4%), fatigue (14.5% vs 10.4%), hypokalemia (5.8% vs 4.5%), pneumonia (0.0% vs 6.0%), peripheral neuropathy (4.8% vs 0.0%),etc. Duration of maintenance, the AEs in the ET group were significantly lighter, just like anemia (0.0% vs 28.4%), leukopenia (5.8% vs 17.8%), neutropenia (5.8% vs 16.4%), thrombocytopenia (2.9% vs 22.4%) et al., the non-hematologic toxicities were HFS (0.0% vs 23.9%), increased ALT (4.3% vs 16.4%), increased AST (5.8% vs 16.4%), increased bilirubin (0.0% vs 10.4%), peripheral neuropathy (5.8% vs 0.0%). Moreover, the toxicities of grade 3/4 were in the CT maintenance group, anemia was 1 case (1.5%), neutropenia 2 cases (2.99%), HFS 5 Case (7.5%) and increased AST in 1 case (1.5%). The ET maintenance group had not any grade 3/4 AEs. Conclusions: For HR+ and HER2- MBC, after 1st-line salvage combined chemotherapy, HT maintenance therapy is superior to chemotherapy (capecitabine) maintenance in terms of efficacy and safety. But, if toxicity is well managed, the safety is still tolerated during chemotherapy maintenance. Therefore, in the post-CDK4/6 period, chemotherapy is still an option. Clinical trial information: NCT02597868.