Fixed low-dose nab-paclitaxel with tislelizumab in non-metastatic bladder cancer: A post-hoc analysis of dose expose in TRUCE-01 and TRUCE-02 trials.

Abstract

768 Background: Although PD-1 immune checkpoint inhibitors (PD-1 ICIs) show efficacy in bladder cancer, exploring effective immunomodulatory strategies remains necessary. Nab-paclitaxel has demonstrated immunomodulatory properties that may enhance the effectiveness of PD-1 ICIs. Herein, we conducted a post-hoc analysis of two phase II trials conducted in our centre to evaluate whether body surface area (BSA)–adjusted exposure to fixed low-dose nab-paclitaxel affects efficacy or safety when combined with tislelizumab, a type of PD-1 ICIs. Methods: Patients (pts) with non-metastatic muscle-invasive bladder cancer (MIBC) or very high-risk non-muscle-invasive bladder cancer (NMIBC) from the TRUCE-01 (NCT04730219) and TRUCE-02 (NCT04730232) trials were included. All pts received ≥3 cycles of tislelizumab (200 mg iv Q3W) plus fixed-dose nab-paclitaxel (200 mg iv Q3W). The nab-paclitaxel dose per m² (NP-DPM) was calculated as 200 mg divided by BSA (Mosteller formula). Pts were grouped by NP-DPM tertiles: low ( < 102 mg/m²), medium (102–117 mg/m²), and high ( > 117 mg/m²). The primary endpoint was complete response (CR, defined as no residual tumor on pathology). Secondary endpoints included overall survival (OS), metastasis-free survival (MFS), cancer-specific survival (CSS) and nab-paclitaxel–related adverse events (NPRAEs). Results: Of 106 evaluable patients we finally included, the median NP-DPM was 106 mg/m² (IQR 102–117). The CR rates were 63.0%, 56.6%, and 57.7% in the low-, medium-, and high-dose groups, respectively (p = 0.902), with no significant differences within MIBC or NMIBC subgroups. At a median follow-up of 34.4 months, no significant differences were observed in OS (p = 0.051), MFS (p = 0.216), or CSS (p = 0.112) among different NP-DPM groups. Peripheral sensory neuropathy was the only NPRAEs that significantly increased with NP-DPM (0% vs 3.8% vs 19.2%, p = 0.009). Other NPRAEs (alopecia, fatigue, cytopenias) did not differ between groups. Conclusions: Fixed low-dose nab-paclitaxel combined with tislelizumab achieved robust and consistent responses across BSA-based exposure groups, with a favourable safety profile. These results support further evaluation of this chemotherapy–immunotherapy combination as a potential treatment strategy for non-metastatic bladder cancer.