An update on immunotherapy options for urothelial cancer

ABSTRACT

Introduction: The efficacy of immune checkpoint inhibitors has been shown in many malignancies. Urothelial cancers have a high mutational load and also express a high level of PD-L1. Therefore, the use of immune checkpoint inhibitors (ICIs) in various treatment lines is being intensively investigated in urothelial cancers.

Area covered: In this review article, we aimed to summarize the development of immune checkpoint inhibition in urothelial cancers. We also provide updated and comprehensive data about the use of ICIs in the second-line and first-line treatment of patients who are ineligible for cisplatin. We also summarize ongoing trials and the results of published trials. A literature search was made using PubMed, Medline, and ASCO and ESMO Annual Meetings abstracts by using the following search terms: nivolumab, pembrolizumab, atezolizumab, avelumab, durvalumab, and urothelial cancer.

Expert opinion: ICIs as a monotherapy are effective for the first-line treatment of the patients with advanced urothelial carcinoma who are ineligible for cisplatin, and also patients who are pre-treated with platinum-based chemotherapy. The results of trials investigating the efficacy of the combination of ICIs and chemotherapy in the first-line setting are awaited; it remains unclear as to whether this combination may become the standard first-line treatment in advanced urothelial cancer.

KEYWORDS:

• Immune checkpoint inhibition
• PD-1
• PD-L1
• urothelial cancer

Article Highlights

• Urothelial cancer is one of the diseases that has high tumor mutation load and high levels of PD-L1 expression.

• In first-line settings, monotherapy of atezolizumab and pembrolizumab was detected as effective treatment in patients with advanced urothelial carcinoma, and was also approved in patients who are not candidates for cisplatin-based chemotherapy or have a tumor with high PD-L1 expression and also are not candidate for any platinum-based chemotherapy.

• In the second-line setting, pembrolizumab, nivolumab, durvalumab, and avelumab were approved in patients whose disease progressed after first-line platin-based chemotherapy. However, the phase 3 Imvigor 211 trial that investigated the efficacy of atezolizumab failed. On the other hand, OS was superior in the subgroup with high TMB and also the ITT population.

• Immune checkpoint inhibitors have many advantages compared with chemotherapy such as long duration of response, low adverse event profile, and efficacy in cisplatin-ineligible patients. On the other hand, a low response rate may become an essential issue for patients who need a rapid response.

• PD-L1 is the most commonly used biomarker in many trials, including those on urothelial cancer. However, the search for new biomarkers is still in progress.

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Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.