Abstract PS1-09-24: Efficacy and safety of Albumin-Bound Paclitaxel (SYHX2011) in Patients with Advanced Breast Cancer: A Multicenter, Randomized, Double-blind Phase III study

Abstract Background: Paclitaxel is a highly active chemotherapy agent as the standard treatment for advanced breast cancer. Albumin-bound paclitaxel is SPARC mediated enhanced paclitaxel distribution in tumor by high binding affinity to albumin, with high incidence of rash after treatment. SYHX2011 is a novel albumin-bound paclitaxel, with most non-particular human albumin replaced with mannitol and sucrose. This study aimed to compare SYHX2011 and paclitaxel for injection (albumin-bound) (PAB) outcomes in the patients with breast cancer. Methods: This is a multicenter, randomized, double-blind, phase III trial (NCT05753865). Patients with histologically/cytologically confirmed unresectable locally advanced or metastatic breast cancer were randomized in a 1:1 ratio to SYHX2011 (260 mg/m2) or PAB (260 mg/m2) administered every 3 weeks by intravenous infusion. Randomization was stratified by previous taxanes use and rash occurrence (previous taxanes with rash or previous taxanes with no rash or no previous taxanes), as well as previous chemotherapy for the advanced disease (yes or no). The primary endpoint was objective response rate (ORR) assessed by independent review committee (IRC). Noninferiority was verified if the lower confidence bound of 95% confidence interval (CI) in rate ratio (RR) was higher than 0.75; and superiority would subsequently be evaluated and considered to be confirmed if it was higher than 1. Key secondary endpoint was incidence of rash during the first two administration cycles and the whole cycles. Results: 459 patients were enrolled, including 229 in the SYHX2011 group and 230 in the PAB group. The baseline demographic and disease characteristics were well balanced between two groups. The median (range) age was 56.0 years (27-84). 321 (69.9%) patients received previous treatment with taxanes, of which 317 (69.0%) without a history of rash during the treatment. 129 (28.1%) patients had previous chemotherapy for the advanced disease. The ORR assessed by IRC were 35.8% (95%CI 29.4-42.6) in the SYHX2011 group and 25.8% (95%CI 20.2-32.1) in the PAB group (RR=1.38, 95%CI 1.04-1.84; P=0.0124), indicating that SYHX2011 was noninferior to PAB. The superiority of SYHX2011 over PAB was also confirmed. The incidence of rash during the first two administration cycles in the SYHX2011 group was lower compared with those in the PAB group (13.6% vs. 34.3%, adjusted RR=0.40 [95%CI 0.275-0.577, P