Abstract

Although immune-mediated therapies have been used in genitourinary (gu) malignancies for decades, recent advances with monoclonal antibody checkpoint inhibitors (cpis) have led to a number of promising treatment options. In renal cell carcinoma (rcc), cpis have been shown to have benefit over conventional therapies in a number of settings, and they are the standard of care for many patients with metastatic disease. Based on recent data, combinations of cpis and antiangiogenic therapies are likely to become a new standard approach in rcc. In urothelial carcinoma, cpis have been shown to have a role in the second-line treatment of metastatic disease, and a number of clinical trials are actively investigating cpis for other indications. In other gu malignancies, such as prostate cancer, results to date have been less promising. Immunotherapies continue to be an area of active study for all gu disease sites, with several clinical trials ongoing. In this review, we summarize the current evidence for cpi use in rcc, urothelial carcinoma, prostate cancer, testicular germ-cell tumours, and penile carcinoma. Ongoing clinical trials of interest are highlighted, as are the challenges that clinicians and patients will potentially face as immune cpis become a prominent feature in the treatment of gu cancers.

Highlights

  • The genitourinary malignancies constitute a heterogeneous group of diseases affecting the kidney, renal collecting system, bladder, prostate, testes, and penis, with each malignancy having a distinct biology and clinical outcomes

  • The orr was significantly improved at 42% in the ipilimumab–nivolumab arm compared with 27% in the sunitinib arm (p < 0.001), with a cr rate of 9% in the cpi arm

  • A number of phase iii trials using cpis are ongoing in the first-line setting, including a trial comparing nivolumab– cabozantinib with sunitinib (NCT03141177), and a 3-arm trial of combination lenvatinib–pembrolizumab compared with lenvatinib–everolimus and with sunitinib alone (NCT02811861)

Read more

Summary

BACKGROUND

The genitourinary (gu) malignancies constitute a heterogeneous group of diseases affecting the kidney, renal collecting system, bladder, prostate, testes, and penis, with each malignancy having a distinct biology and clinical outcomes. In the itt group (comprising all randomized patients, including 23% of the study population with favourable-risk disease), an os benefit was observed for ipilimumab–nivolumab compared with sunitinib (hr: 0.68; 99.8% ci: 0.49 to 0.95), no significant benefit in pfs or orr was observed. A number of phase iii trials using cpis are ongoing in the first-line setting, including a trial comparing nivolumab– cabozantinib with sunitinib (NCT03141177), and a 3-arm trial of combination lenvatinib–pembrolizumab compared with lenvatinib–everolimus and with sunitinib alone (NCT02811861) Both studies will use pfs in all-comers as the primary outcome. 49.4% of patients in the chemotherapy arm experienced grade 3 or greater adverse effects, with 11.0% requiring toxicity-related treatment discontinuation Based on those results, pembrolizumab was approved by Health Canada in the second-line setting. The primary endpoint of os was assessed in a hierarchical fashion: first in the population

Objective response rate
Findings
SUMMARY
Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call