Neoadjuvant gemcitabine-cisplatin plus tislelizumab in persons with resectable muscle-invasive bladder cancer: a multicenter, single-arm, phase 2 trial.

Programmed death 1 blockade (tislelizumab) has been approved for metastatic urothelial carcinoma but not as part of neoadjuvant therapy for muscle-invasive bladder cancer (MIBC). In this multicenter single-arm trial (ChiCTR2000037670), 65 participants with cT2-4aN0M0 MIBC received neoadjuvant gemcitabine-cisplatin plus tislelizumab; 57 of them underwent radical cystectomy (RC). The primary endpoint of pathologic complete response (pCR) rate was 50.9% (29/57, 95% confidence interval (CI) 37.3-64.4%) and the pathologic downstaging (secondary endpoint) rate was 75.4% (43/57, 95% CI 62.2-85.9%) in participants undergoing RC. Genomic and transcriptomic analyses revealed three MIBC molecular subtypes (S): S1 (immune-desert) with activated cell-cycle pathway, S2 (immune-excluded) with activated transforming growth factor-β pathway and S3 (immune-inflamed) with upregulated interferon-α and interferon-γ response. Post hoc analysis showed pCR rates of 16% (3/19, S1), 77% (10/13, S2) and 80% (12/15, S3) (P = 0.006). In conclusion, neoadjuvant gemcitabine-cisplatin plus tislelizumab for MIBC was compatible with an enhanced pCR rate.

Li K ，Zhong W ，Fan J ，Wang S ，Yu D ，Xu T ，Lyu J ，Wu S ，Qin T ，Wu Z ，Xu L ，Wu K ，Liu Z ，Hu Z ，Li F ，Wang J ，Wang Q ，Min J ，Zhang Z ，Yu L ，Ding S ，Huang L ，Zhao T ，Huang J ，Lin T ... -  《Nature Cancer》

Bladder-sparing treatment using tislelizumab combined with gemcitabine/cisplatin in selected patients with muscle-invasive bladder cancer: a real-world study.

To retrospectively evaluate the tislelizumab-based chemoimmunotherapy combined with gemcitabine/cisplatin for bladder-sparing in patients with muscle-invasive bladder cancer (MIBC). Forty-five patients who received bladder-sparing treatment or radical cystectomy (RC) for MIBC (cT2-T4a, NxM0) were retrospectively enrolled. All patients received maximal transurethral resection of bladder tumor (mTURBT), followed by four cycles of chemo-immunotherapy with tislelizumab (PD-L1 inhibitor), gemcitabine, and cisplatin. Clinical efficacy was evaluated to compare the benefit of bladder-sparing treatment on clinical CR (cCR) and RC for non-cCR patients. The primary outcomes were bladder intact disease-free survival (BIDFS) and overall survival (OS), and the secondary outcomes were adverse effects. The PD-L1 status and molecular subtypes of tumors were analyzed. The overall survival rate was 88.8% (95%CI: 79.6%, 98.0%) at 12 months, 85.7% (95%CI: 74.9%, 96.5%) at 18 months, and 66.6% (95%CI: 45.2%, 88.0%) at 24 months. Twenty-nine patients (64.4%) achieved cCR and their OS rate was 96.6% (95%CI: 89.9%, 100%). Sixteen patients were in the non-cCR group, and their OS rate was 75.0% (95%CI: 53.8%, 96.2%) at 12 months, 65.6% (95%CI: 40.3%, 90.9%) at 18 months, and 52.5% (95%CI: 21.9%, 83.1%) at 24 months. The BIDFS rate for patients who received bladder-sparing treatment was 96.0% (95%CI: 88.4%, 100%) from 12 to 24 months. Four patients (8.8%) were PD-L1 positive and 41 patients (91.2%) were PD-L1 negative. Our retrospective study of patients with MIBC suggests that tislelizumab-based neoadjuvant therapy was a safe and effective bladder-sparing treatment.

Luo C ，Luo S ，Wusimanjiang W ，Wang Z ，Liu P ，Wang B ，Yuan D ，Lin H ，Xu A ，Deng N ，Wu K ，Zhu X ，Xu P ，Chen J ，Huang B ... -  《-》

Phase II Study of Gemcitabine and Split-Dose Cisplatin Plus Pembrolizumab as Neoadjuvant Therapy Before Radical Cystectomy in Patients With Muscle-Invasive Bladder Cancer.

Rose TL ，Harrison MR ，Deal AM ，Ramalingam S ，Whang YE ，Brower B ，Dunn M ，Osterman CK ，Heiling HM ，Bjurlin MA ，Smith AB ，Nielsen ME ，Tan HJ ，Wallen E ，Woods ME ，George D ，Zhang T ，Drier A ，Kim WY ，Milowsky MI ... -  《-》

Retrospective analysis of the efficacy and safety of neoadjuvant gemcitabine and cisplatin in muscle-invasive bladder cancer.

Meleis L ，Moore R ，Inman BA ，Harrison MR ... -  《-》

Neoadjuvant Atezolizumab With Gemcitabine and Cisplatin in Patients With Muscle-Invasive Bladder Cancer: A Multicenter, Single-Arm, Phase II Trial.

Funt SA ，Lattanzi M ，Whiting K ，Al-Ahmadie H ，Quinlan C ，Teo MY ，Lee CH ，Aggen D ，Zimmerman D ，McHugh D ，Apollo A ，Durdin TD ，Truong H ，Kamradt J ，Khalil M ，Lash B ，Ostrovnaya I ，McCoy AS ，Hettich G ，Regazzi A ，Jihad M ，Ratna N ，Boswell A ，Francese K ，Yang Y ，Folefac E ，Herr HW ，Donat SM ，Pietzak E ，Cha EK ，Donahue TF ，Goh AC ，Huang WC ，Bajorin DF ，Iyer G ，Bochner BH ，Balar AV ，Mortazavi A ，Rosenberg JE ... -  《-》