Table 1 Completed phase II or III clinical studies in genitourinary malignancies

HD-IL2 [11]

Metastatic RCC, first line

600,000 or 720,000 IU/kg every 8 hourly up to 14 consecutive doses for 5 days every 2 weeks. Four to 6 cycles of treatment based on clinical and radiographic responses

HD-IL2 stimulates proliferation and differentiation of T, B, and NK lymphocytes. It causes recruitment of tumor-infiltrating lymphocytes at tumor sites

ORR was 14% with complete response (CR) seen in 5% patients and partial response (PR) in 9% of patients. Median duration of PR was 19 months

Capillary leak syndrome, hypotension, fever and chills, anemia, nausea and vomiting, diarrhea, mental status changes, elevated liver enzymes and bilirubin, elevated BUN and creatinine, dyspnea, and pruritus

IFN-α plus bevacizumab vs. IFN-α [14, 15]

Metastatic RCC, first line

IFN-α (9 million units SC 3 times/week) with bevacizumab (10 mg/kg intravenously every 2 weeks) vs. IFN-α

IFN-α is a cytokine with immune-modulatory and anti-proliferative activity

Median PFS was 8.5 months for bevacizumab plus IFN-α (95% CI, 7.5 to 9.7 months) compared to 5.2 months (95% CI, 3.1 to 5.6 months) for IFN-α monotherapy.

Median OS (primary end point) 18.3 months for bevacizumab plus IFN-α compared to 17.4 months for IFN-α monotherapy

Fatigue, anorexia, nausea, proteinuria, neutropenia, and hypertension

Bevacizumab plus IFN-α vs. IFN-α plus placebo [16]

Metastatic RCC, first line

Bevacizumab (10 mg/kg every 2 weeks) with IFN-α (9 MIU SC 3 times/week) or same dose IFN-α with placebo

IFN-α is a cytokine with immune-modulatory and anti-proliferative activity

Median OS (primary end point) with bevacizumab/IFN-α was 23.3 months vs. 21.3 months.

At interim analysis, median PFS was significantly longer with bevacizumab/IFN-α vs. IFN-α/placebo (10.2 vs. 5.4 months and ORR 31 vs. 13%, respectively

Fatigue, asthenia, and neutropenia with IFN-α and proteinuria, hypertension, GI perforation, and bleeding with bevacizumab. There were 2% deaths related to treatment on both arms.

Nivolumab vs. everolimus [18]

Metastatic RCC, Second line and beyond

Nivolumab 3 mg/kg of body weight every 2 weekly vs. oral 10 mg everolimus tablet daily.

Programmed death 1 (PD-1) checkpoint inhibitor

Median OS was 25.0 months with nivolumab compared to 19.6 months with everolimus.

Median PFS 4.6 months with nivolumab compared to 4.4 with everolimus. The ORR was superior with nivolumab than everolimus

Nivolumab arm: fatigue, nausea, pruritus, diarrhea, anorexia, and rash

Atezolizumab [33, 34]

Metastatic or advanced bladder cancer after platinum-based chemotherapy

1200 mg fixed dose intravenous every 3 weeks

Programmed death-1 ligand (PD-L1) inhibitor

ORR 15% in all patients with a complete response rate of 5%. Median duration of response not reached. Median PFS was 2.1 months and median OS 7.9 months

Fatigue, nausea, poor appetite pruritus, anemia, hypertension, pneumonitis, increased AST, ALT, rash, and dyspnea

Sipuleucel-T vs. placebo [40, 41]

Metastatic CRPC

Three cycles intravenously every 2 weeks

Dendritic cells activated using a fusion protein (PA2024) consisting of prostatic acid phosphatase (PAP) and GM-CSF

Median OS was 25.8 months with sipuleucel compared to 21.7 months with placebo. PFS was not different between the two arms

Sipuleucel-T: chills, fever, fatigue, back pain, and headache