Introduction: The PURE-01 and ABACUS studies has elucidated the administration of neoadjuvant immune checkpoint inhibitors in muscle-invasive bladder cancer (MIBC), with efficacy comparable to chemotherapy and less adverse events. However, the role of PD-1/PD-L1 inhibitor combining with chemotherapy remains unclear. We conduct a study to evaluate the outcome of pts treated with neoadjuvant PD-1 combined with second-line chemotherapy for MIBC.
Methods: TRUCE-01 is a phase II study of Tislelizumab combined with Nab-Paclitaxel before cystectomy or complete TURBT (cTURBT): the primary endpoint is pathologic complete response (pT0). Pts with clinical stage T2-4aN0-1M0 received tislelizumab 200mg on days 1 plus paclitaxel 200mg on days 2 every 3 weeks (Q3W) x 3 cycles followed by radical cystectomy or cTURBT. Biomarker analyses included programmed death-ligand 1 (PD-L1) expression using the combined positive score (CPS; Dako 22C3 pharmDx assay) and tumor mutational burden (TMB). Comparisons between PD-L1 expression subgroups were made via Fisher’s exact tests for categorical variables.
Results: Between July 2020 and July 2021, 30 pts have completed neoadjuvant treatment and received radical cystectomy(n=9, 31%) or cTURBT(n=21, 69%). Finally, 16 pts achieved pT0 (53.3%; 95% CI, 36.7% to 73.3%). As a secondary end point, downstaging to pT <2 was achieved in 21 pts (70%; 95% CI, 53.3% to 86.7%). There were 2 pts experienced grade 3-4 adverse events (CTCAE), a grade 3 rash and a grade 4 acute renal failure, both of them recovered after treating by corticosteroid. In addition, The most common grade 1-2 adverse events include alopecia (96%), fatigue (63%), hyperglycemia (33%), rash (27%),fever (17%), and Creatinine increased (13%) . There was no significant correlation between PD-L1 expression and therapeutic effect. pT0 was achieved in 8 pts (61.5%) with PD-L1 positive compared with 8 pts (47%) with PD-L1 negative (P = .484). As for tumor mutational burden (TMB), response pts show high lever (P = .067).
Conclusions: The early efficacy data further support the role of Tislelizumab combined with Paclitaxel as neoadjuvant therapy in MIBC, benefiting them in a higher rate of pCR without increasing frequency of serve AEs. PD-L1 expression has no obvious correlation with the efficacy of immunotherapy combined chemotherapy. Patients with high TMB are more likely to respond to neoadjuvant therapy. Enrollment is ongoing.
Source of Funding: The present study received financial support from the the Natural Science Foundation Project of Tianjin (grant no. 18PTLCSY00010).
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