Albumin-Bound Paclitaxel (SYHX2011) in Patients with Advanced Breast Cancer: A Multicenter, Randomized, Double-Blind,...

Background: SYHX2011 is a novel albumin-bound paclitaxel, in which most nonparticulate human albumin is replaced with mannitol and sucrose. This study aimed to compare SYHX2011 and paclitaxel for injection (albumin-bound) (PAB) in patients with breast cancer. Methods: Patients with histologically or cytologically confirmed unresectable locally advanced or metastatic breast cancer were randomly assigned to receive SYHX2011 (260 mg/m²) or PAB (260 mg/m²) intravenously once every 3 weeks, stratified by prior taxane use and rash history (prior taxane with rash, prior taxane without rash, or no prior taxane), as well prior lines of chemotherapy for advanced disease (0 or ≥1). The primary endpoint was objective response rate assessed by an independent review committee. Noninferiority was to be declared if the lower bound of the 95% confidence interval (CI) for the rate ratio exceeded 0.75; if the lower bound exceeded 1, superiority would subsequently be tested and considered confirmed. Results: In this multicenter, randomized, double-blind, phase III trial across 56 centers in China, 621 patients were screened between 2023 April 23 and 2024 March 21, of whom 459 patients were randomized to SYHX2011 (n = 229) or PAB (n = 230). The confirmed objective response rate assessed by an independent review committee was 35.8% (95% CI 29.4% to 42.6%) for SYHX2011 and 25.8% (95% CI 20.2% to 32.1%) for PAB (rate ratio = 1.38, 95% CI 1.04 to 1.84; one-sided P = 0.012), indicating that SYHX2011 was noninferior to PAB. The superiority of SYHX2011 over PAB was also confirmed. SYHX2011 showed a lower incidence of rash compared with PAB during the first 2 administration cycles (13.6% vs. 34.3%) and all treatment cycles (16.2% vs. 42.6%). Treatment-related adverse events (TRAEs) occurred in 98.2% of patients receiving SYHX2011 and 98.3% of patients receiving PAB. In the SYHX2011 group, 111 (48.7%) patients experienced grade ≥3 TRAEs, compared with 101 (43.9%) patients in the PAB group. The most common grade ≥3 TRAEs were neutropenia, leukopenia, and peripheral sensory neuropathy. The median investigational drug reconstitution time was 2.0 min for SYHX2011 and 11.0 min for PAB. Conclusions: SYHX2011 demonstrated greater therapeutic benefits than PAB and significantly reduced the incidence of rash. Additionally, it could offer greater convenience in clinical application, providing advanced breast cancer patients with more effective and safer treatment options. Trial registration: ClinicalTrials.gov identifier: NCT05753865. Date of registration: 2023 February 22.