Metronomic paclitaxel and cisplatin chemotherapy for metastatic breast cancer: insights from a target trial emulation

• DOI: 10.1016/j.lanwpc.2024.101457
• Publication Date: 2025-02-17T23:43:21Z
• Authors: Yaorong Li; Liang Zhu; Wenjin Yin; Yaohui Wang; Jingsong Lu
• Keywords: Public aspects of medicine; RA1-1270

Background: The management of metastatic breast cancer (MBC) poses a significant clinical challenge due to its high incidence of drug resistance and the limited efficacy of conventional therapies. This study aimed to assess the real-world effectiveness of metronomic chemotherapy with paclitaxel and cisplatin in patients with MBC, utilizing a target trial emulation framework to enhance the generalizability of findings. Methods: This retrospective cohort study aimed to emulate a randomized clinical trial comparing metronomic chemotherapy of low dose weekly paclitaxel and cisplatin (DP group) with other therapies (control group). We recruited women aged over 18 years with metastatic breast cancer who had received at least one line therapy after metastasis at Breast Cancer Center, Renji Hospital, School of Medicine, Shanghai Jiao Tong University. Propensity score matching (1:3) was utilized to balance baseline characteristics between two groups, including hormone receptor (HR) status, human epidermal growth factor receptor 2 (HER2) status, age, prior treatments, and disease-free interval. Target trial emulation methods including cloning, censoring, and inverse probability of censoring weights were employed to mitigate biases and improve causal inference. The primary endpoint was progression-free survival (PFS). This study was approved by Renji Hospital Ethics Committee (approval ID: KY2024-159-B) and registered with Chinese Clinical Trial Registry (ChiCTR2400089679). Findings: Between April 1, 2014, and January 1, 2023, A total of 524 patients were enrolled in the study. Following matching procedures, analysis was conducted on a cohort consisting of 83 patients in the DP group and 230 patients in the control group. In this matched naïve population, the DP group (13.5 months [95% CI 10.3-16.6]) demonstrated a significant improvement in PFS compared to the control group (7.9 months [95% CI 6.7-9.1], Hazard ratio [HR] 0.77, 95% CI 0.60-0.99, p=0.048). These results remained consistent even after target trial emulation, with the DP group achieving a median PFS of 14.1 months (95% CI 13.3-16.6), while it was only 8.3 months (95% CI 8.0-8.6) for the control group (HR 0.59, 95% CI 0.54-0.64, p<0.0001). Among patients receiving first-line therapy, metronomic DP treatment conferred the greatest benefit by extending median PFS to an impressive duration of 19.2 months compared with just 8.6 months for other treatments (HR 0.47, 95% CI 0.43-0.52, p<0.0001) in the emulated population. Sensitivity analyses further supported these robust findings across subgroups including HR-positive/HER2-negative patients and those with visceral metastases. Interpretation: To our knowledge, this cohort study is the first study to demonstrate that metronomic chemotherapy with DP offers a novel and clinically meaningful benefit in improving PFS for patients with MBC, particularly in first-line treatment settings. By employing target trial emulation, this analysis provides fresh insights into the effectiveness of DP in real-world scenarios. Funding: None.