Efficacy and Safety of Neoadjuvant Immunotherapy in Combination with Neoadjuvant Gemcitabine and Cisplatin - Expert Commentary

For patients with muscle-invasive bladder cancer (MIBC), the gold standard for treatment is cisplatin-based neoadjuvant chemotherapy followed by radical cystectomy. However, the response to neoadjuvant chemotherapy varies significantly, and additional regimens that enhance the efficacy of neoadjuvant chemotherapy are needed.

Kim et al. sought to test the activity and efficacy of nivolumab in MIBC patients receiving neoadjuvant gemcitabine and cisplatin (GC). This study was a single-center, prospective, phase II study. The researchers recruited 51 MIBC patients who were eligible for cisplatin, had not previously received chemotherapy for MIBC, were eligible to receive radical cystectomy, and did not exhibit lymph node involvement. Patients first underwent transurethral resection of bladder tumor (TURBT) to confirm their tumor stage was T2-T4a, as this was an additional inclusion criterion.

After treatment, 30 patients had clinical complete response. Of these, 12 opted out of surgery and were treated with chemoradiotherapy. Accordingly, 34 patients underwent radical cystectomy. The median duration between the end of treatment and surgery was 36 days. No patients died within 3 months of surgery. After surgery, 12 patients had pathologic complete response (ypT0), 4 ypTis, 3 ypTa, 3 ypT1, and 12 ypT2/T3. In addition, two patients had lymph node involvement. The median follow-up duration was 24 months, during which 12 patients experienced disease recurrence. The sites of recurrence were the urinary tract (7 patients), lymph nodes (3 patients), and distant sites (2 patients). The disease-free survival rates were 90% at 12 months and 73% at 24 months. In terms of PD-L1 status, 41% of patients were positive at baseline. However, pre-operative PD-L1 levels were not correlated with response or downstaging rate. After surgery, 29% of patients had PD-L1-positive tumors. It is important to note that PD-L1 expression was only tested in 21 patients after surgery. The most frequently reported side effects were fatigue, nausea, and pruritus. However, six patients required a reduction in the chemotherapy dose.

Overall, nivolumab treatment in combination with GC was feasible. However, the lack of a control group makes it challenging to define the contributions of different components of this combinatorial regimen. These results add to the emerging data on the role of neoadjuvant immunotherapy for patients with MIBC.

Written by: Bishoy M. Faltas, MD, Director of Bladder Cancer Research, Englander Institute for Precision Medicine, Weill Cornell Medicine


  1. Kim H, Jeong BC, Hong J, et al. Neoadjuvant Nivolumab plus Gemcitabine/Cisplatin Chemotherapy in Muscle-Invasive Urothelial Carcinoma of the Bladder [published online ahead of print, 2022 Oct 6]. Cancer Res Treat. 2022;10.4143/crt.2022.343. doi:10.4143/crt.2022.343

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