Adjuvant immunotherapy

A randomized controlled trial (Checkmate 274 [NCT02632409]) compared nivolumab with placebo in 709 patients with pathological T3, T4, or node-positive muscle-invasive urothelial carcinoma who had undergone radical cystectomy. Of note, the patients in this trial had either received preoperative cisplatin-based chemotherapy, refused postoperative cisplatin-based chemotherapy, or been deemed unfit for cisplatin-based chemotherapy.[24][Level of evidence A1]

A randomized controlled trial (Checkmate 274 [NCT02632409]) compared nivolumab with placebo in 709 patients with pathological T3, T4, or node-positive muscle-invasive urothelial carcinoma who had undergone radical cystectomy. Of note, the patients in this trial had either received preoperative cisplatin-based chemotherapy, refused postoperative cisplatin-based chemotherapy, or been deemed unfit for cisplatin-based chemotherapy.[24][Level of evidence A1]

At a median follow-up of 36.1 months, the OS was 69.6 months (95% CI, 58.1–not estimable [NE]) in the nivolumab arm and 50.1 months (95% CI, 38.2–NE) in the placebo arm (HR, 0.76; 95% CI, 0.61–0.96). In patients with programmed death-ligand 1 (PD-L1) expression of 1% or higher (approximately 40% of all enrolled patients), the median OS was not reached in either arm (HR, 0.56; 95% CI, 0.36–0.86).

A randomized controlled trial (Checkmate 274 [NCT02632409]) compared nivolumab with placebo in 709 patients with pathological T3, T4, or node-positive muscle-invasive urothelial carcinoma who had undergone radical cystectomy. Of note, the patients in this trial had either received preoperative cisplatin-based chemotherapy, refused postoperative cisplatin-based chemotherapy, or been deemed unfit for cisplatin-based chemotherapy.[24][Level of evidence A1]

The median DFS was 22.0 months (95% CI, 18.8–36.9) in the nivolumab arm and 10.9 months (95% CI, 8.3–15.2) in the placebo arm (HR, 0.71; 95% CI, 0.58–0.86). In patients with PD-L1 expression of 1% or greater, the median DFS was 52.6 months (95% CI, 25.8–NE) in the nivolumab arm and 8.4 months (95% CI, 5.6–17.9) in the placebo arm (HR, 0.52; 95% CI, 0.37–0.72).

A randomized controlled trial (Checkmate 274 [NCT02632409]) compared nivolumab with placebo in 709 patients with pathological T3, T4, or node-positive muscle-invasive urothelial carcinoma who had undergone radical cystectomy. Of note, the patients in this trial had either received preoperative cisplatin-based chemotherapy, refused postoperative cisplatin-based chemotherapy, or been deemed unfit for cisplatin-based chemotherapy.[24][Level of evidence A1]

In patients with PD-L1 expression of less than 1% in the intent-to-treat population, the HR for median DFS for nivolumab compared to placebo was 0.84 (95% CI, 0.66–1.06). In patients with PD-L1 expression of less than 1% and muscle-invasive bladder cancer (79% of enrolled patients), the median DFS was 18.3 months (95% CI, 14.1–22.4) in the nivolumab arm and 9.7 months (95% CI, 7.4–16.6) in the placebo arm (HR, 0.74; 95% CI, 0.56–0.97). OS data were not included in the supplement for patients with PD-L1 expression of less than 1%.

A randomized controlled trial (Checkmate 274 [NCT02632409]) compared nivolumab with placebo in 709 patients with pathological T3, T4, or node-positive muscle-invasive urothelial carcinoma who had undergone radical cystectomy. Of note, the patients in this trial had either received preoperative cisplatin-based chemotherapy, refused postoperative cisplatin-based chemotherapy, or been deemed unfit for cisplatin-based chemotherapy.[24][Level of evidence A1]

Grade 3 or higher adverse events were seen in 42.7% of patients in the nivolumab arm and 36.8% of patients in the placebo arm. High-grade treatment-related adverse events were seen in 18.2% of patients in the nivolumab arm and 7.2% of patients in the placebo arm. The most common adverse events were pruritus, fatigue, and diarrhea, while the most common grade 3 or higher adverse events were elevated lipase or amylase, diarrhea, colitis, and pneumonitis. Two patients in the nivolumab arm died of pneumonitis, and one patient died of a bowel perforation.

A randomized controlled trial (AMBASSADOR [NCT03244384]) compared adjuvant pembrolizumab with observation in 702 patients. Patients had undergone radical cystectomy and had positive margins, node-positive disease, and either pathological T2 or higher stage disease (if neoadjuvant cisplatin-based chemotherapy was received) or T3 or higher disease (if no neoadjuvant chemotherapy had been received).[25][Level of evidence B1]

A randomized controlled trial (AMBASSADOR [NCT03244384]) compared adjuvant pembrolizumab with observation in 702 patients. Patients had undergone radical cystectomy and had positive margins, node-positive disease, and either pathological T2 or higher stage disease (if neoadjuvant cisplatin-based chemotherapy was received) or T3 or higher disease (if no neoadjuvant chemotherapy had been received).[25][Level of evidence B1]

At a median follow-up of 44.8 months, the DFS was 26.9 months (95% CI, 20.0–40.7) in the pembrolizumab arm and 14.2 months (95% CI, 11.0–20.2) in the observation arm (HR, 0.73; 95% CI, 0.59–0.90).

A randomized controlled trial (AMBASSADOR [NCT03244384]) compared adjuvant pembrolizumab with observation in 702 patients. Patients had undergone radical cystectomy and had positive margins, node-positive disease, and either pathological T2 or higher stage disease (if neoadjuvant cisplatin-based chemotherapy was received) or T3 or higher disease (if no neoadjuvant chemotherapy had been received).[25][Level of evidence B1]

In patients with a PD-L1 combined positive score (CPS) of at least 10 (57.5% of all enrolled patients), the median DFS was 36.9 months (95% CI, 27.2–NE) in the pembrolizumab arm and 21.0 months (95% CI, 13.6–53.3) in the observation arm (HR, 0.81; 95% CI, 0.61–1.08). In patients with a PD–L1 CPS less than 10 (42.5% of all enrolled patients), the median DFS was 17.3 months (95% CI, 13.2–32.0) in the pembrolizumab arm and 9.0 months (95% CI, 6.9–15.3) in the observation arm (HR, 0.71; 95% CI, 0.53–0.95).

A randomized controlled trial (AMBASSADOR [NCT03244384]) compared adjuvant pembrolizumab with observation in 702 patients. Patients had undergone radical cystectomy and had positive margins, node-positive disease, and either pathological T2 or higher stage disease (if neoadjuvant cisplatin-based chemotherapy was received) or T3 or higher disease (if no neoadjuvant chemotherapy had been received).[25][Level of evidence B1]

The 3-year OS rate was not significantly different, at 60.5% for patients in the pembrolizumab arm and 61.9% for patients in the observation arm (HR, 0.98; 95% CI, 0.76–1.26).

A randomized controlled trial (AMBASSADOR [NCT03244384]) compared adjuvant pembrolizumab with observation in 702 patients. Patients had undergone radical cystectomy and had positive margins, node-positive disease, and either pathological T2 or higher stage disease (if neoadjuvant cisplatin-based chemotherapy was received) or T3 or higher disease (if no neoadjuvant chemotherapy had been received).[25][Level of evidence B1]

Grade 3 or higher adverse events occurred in 50.6% of patients in the pembrolizumab arm and 31.6% of patients in the observation arm.