Initial data from the phase 2 TRUCE-01 trial presented at the 2022 AUA annual Meeting showed that the neoadjuvant combination of the PD-1 inhibitor tislelizumab and nab-paclitaxel (Abraxane) induced a high rate of pathologic complete response (pCR) in patients with muscle-invasive bladder cancer (MIBC).1
Investigators of the single-arm, open-label phase 2 trial (NCT04730219) did not observe an increase in adverse events (AEs) or a correlation of PD-L1 expression with the efficacy of the neoadjuvant therapy. However, high tumor mutation burden (TMB) did show a correlation to response with the combination.
Neoadjuvant treatment with immune checkpoint inhibitors showed comparable efficacy and fewer AEs than chemotherapy in the PURE-01 trial (NCT02736266) of pembrolizumab (Keytruda) and the ABACUS trial (NCT02662309) of atezolizumab (Tecentriq) in MIBC. Although, at this point, the efficacy of combination chemotherapy and PD-1/PD-L1 inhibition has not been determined. This study in patients with MIBC is evaluating the PD-1 inhibitor tislelizumab combined with second-line chemotherapy in the neoadjuvant setting.
In the ongoing TRUCE-01 trial, patients with stage T2-4aN0-1M0 disease were given 200 mg of tislelizumab on day 1 and 200 mg of nab-paclitaxel on day 2 every 3 weeks for 3 cycles, followed by complete transurethral resection of bladder tumor (cTURBT) or radical cystectomy. The Dako 22C3 pharmDx assay was used to conduct biomarker analysis on PD-L1 expression using combined positive score. TMB was also evaluated for the analysis. The primary end point was pCR, defined as the absence of a viable tumor (pT0N0M0).
Thirty patients completed this regimen of neoadjuvant tislelizumab plus nab-paclitaxel and received a radical cystectomy (n = 9) or cTURBT (n = 21) between July 2020 and July 2021. A total of 16 patients achieved pCR (53.3%; 95% CI, 36.7%-73.3%). Downstaging to pT less than 2 occurred in 21 patients (70%; 95% CI, 53.3%-86.7%), which was a secondary end point in this trial.
Patients who responded to therapy had a higher TMB level than those who did not respond (P = .067). No significant correlation was observed between PD-L1 expression and the efficacy of the tislelizumab/nab-paclitaxel combination. Eight patients with PD-L1–positive expression achieved pT0 versus 8 patients with PD-L1–negative expression (P = .484).
In terms of AEs, 1 patient experienced grade 3 rash and 1 patient had grade 4 acute renal failure. After corticosteroid treatment, both patients recovered. Alopecia was observed in 96% of patients, fatigue in 63%, hyperglycemia in 33%, rash in 27%, fever in 17%, and creatinine increase in 13% were the most common grade 1 or 2 AEs.
TRUCE-01 is currently enrolling adult patients with histopathologically confirmed urothelial carcinoma who are planning to receive a cTURBT or radical cystectomy. Patients must have an ECOG performance status of 0 to 2 and an expected survival over more than 12 weeks. Patients who have previously received a PD-1, PD-L1, or CTLA-4 antibody or other immunotherapies are not able to participate in this trial. The trial is located at Tianjin Medical University Second Hospital in Tianjin, China.
1. Hu H, Niu Y, Wang H, et al. Update of TRUCE-01: neoadjuvant tislelizumab combined with nab-paclitaxel for muscle-invasive urothelial bladder carcinoma. Presented at: 2022 American Urological Association Annual Meeting; May 13-16, 2022; New Orleans, LA. Abstract PD10-07.