Tislelizumab a new Tx alternative for very high-risk bladder cancer?

In the phase II pilot TRUCE-02 trial, tislelizumab plus low-dose nab-paclitaxel shows promising clinical antitumour activity and is well tolerated in patients with extensive very high-risk (VHR) non-muscle-invasive bladder cancer (NMIBC) who are ineligible for or decline radical cystectomy (RC).

“The standard of care for VHR NMIBC consists of immediate RC,” said the researchers. However, the procedure is linked to substantial morbidity, mortality, and quality of life impairment, especially for certain patient subgroups (eg, the elderly, frail, or those with significant comorbidities). [Eur Urol 2009;55:164-174; Surg Oncol 2016;25:281-297]

The suboptimal response rates tied to immune checkpoint inhibitors for VHR disease also underscore the need for additional therapeutic innovations to improve outcomes. [Eur Urol 2023;84:536-544; Lancet Oncol 2024;25:720-730]

“Furthermore, the treatment landscape for other VHR NMIBC subgroups remains underexplored, particularly for patients with extensive tumours, highlighting an unmet clinical need … Therefore, there is an urgent need to develop more effective and well-tolerated therapeutic strategies for patients with VHR NMIBC,” the researchers said.

TRUCE-02 comprised 63 patients (median age 67 years, 83 percent men) with visually incomplete resection and/or high-volume high-grade T1 tumours who were ineligible for or declined RC. They received IV tislelizumab 200 mg (day 1) and nab-paclitaxel 200 mg (day 2) Q3W. The median treatment duration was 4.8 months. [Clin Cancer Res 2025;doi:10.1158/1078-0432.CCR-24-3321]

Of the 33 patients evaluated during the interim analysis, 20 achieved a complete response (CR) of high-risk disease. According to the researchers, with the results exceeding the required 14 responses to proceed to stage 2, the study met the criteria to move on to the second phase.

Final efficacy analysis

Fifty-nine patients were included in the efficacy analysis. Of these, 37 achieved a CR of high-risk disease. Over a median follow-up of 23.2 months, the median duration of response (DoR) of high-risk disease was not reached (NR) and the 24-month sustained response rate was 96.3 percent.

Thirty-six achieved a CR of any disease at the initial evaluation. The median DoR of any disease was NR and the 24-month sustained response rate was 91.3 percent.

Seven patients had disease progression, median progression-free survival (PFS) was NR, and the estimated PFS rate was 82.4 percent at 24 months.

Three patients died at data cutoff, median overall survival (OS) was NR, and OS rates were 98.3 percent and 94.6 percent at 12 and 36 months, respectively.

Twelve of the 22 nonresponders underwent RC. Of these, three experienced upstaging. “In patients with extensive VHR NMIBC, the observed progression could partially be caused by inherent extreme risk characteristics,” the researchers explained.

Safety profile

Sixty-three patients were included in the safety analysis. Of these, all but one had any-grade treatment-related adverse events (TRAEs), the most common being alopecia (79 percent) and fatigue (73 percent). Six patients discontinued treatment due to grade 3–4 TRAEs.

Forty-six patients had immune-related AEs (irAEs). The most frequent grade 1/2 irAEs were skin reactions (49 percent) and hyperglycaemia (25 percent). Eight patients had grade 3 irAEs, including adrenal insufficiency, hepatitis, and skin reactions.

“Importantly, no new or unexpected safety signals were identified with this regimen, further supporting its clinical feasibility in this patient population,” said the researchers.

Nonsurgical alternative

There are no established nonsurgical treatment alternatives for extensive VHR NMIBC, which are often characterized by bulky tumours that cannot be completely removed via transurethral resection, said the researchers.

“TRUCE-02 is the first nonsurgical clinical trial specifically designed to address the therapeutic needs of this complex patient cohort,” they noted.

“The results provide substantial evidence supporting the clinical effectiveness of tislelizumab combined with low-dose nab-paclitaxel as a [nonsurgical] option for patients with extensive VHR NMIBC who are ineligible for or decline RC,” the researchers concluded.