Perioperative Immunotherapy in Muscle-Invasive Bladder Cancer.

OPINION STATEMENT: There is an acute unmet need to develop novel treatment regimens in the perioperative setting since many patients with muscle-invasive bladder cancer (MIBC) are not eligible for the current standard of care (SOC) neoadjuvant treatment with cisplatin-based chemotherapy. The introduction of immune checkpoint inhibitors (ICIs), both as monotherapy and in combination regimens with other ICIs, chemotherapy, or targeted drugs, may provide safe and clinically effective treatment options that could revolutionize current standard of care. In the neoadjuvant setting, compelling data from phase II clinical trials suggests that single-agent immunotherapy, as well as dual-checkpoint blockade, may emerge as reasonable alternatives to traditional cisplatin-based chemotherapy. Prospective studies combining ICIs with chemotherapy or with antibody-drug conjugates have also demonstrated robust outcomes. However, these studies are not yet practice changing and data from larger randomized studies are needed to confirm this benefit. In the adjuvant setting, nivolumab is the FDA-approved treatment based on a disease-free survival benefit relative to placebo in a randomized trial. However, it will be important to confirm an overall survival benefit of this treatment and to better identify patients who need additional adjuvant treatment based on novel biomarker data. The treatment of muscle-invasive bladder cancer is moving toward the individualization of treatment options based on specific tumor and patient characteristics and away from the one-size-fits-all approach that has dominated this space for the last couple of decades. Emerging biomarker data, such as with ctDNA, suggests that immunotherapy may confer greater benefit to selected patients. Identifying who those patients are will be of paramount importance since additional treatments always come with additional toxicities. On the other hand, the more favorable toxicity profiles of certain immunotherapy-based regimens may make them superior options for some patients who would otherwise be unable to tolerate other systemic regimens. In the near future, it is likely that subsets of patients with MIBC will be receiving treatments with predominantly immunotherapy-based regimens while many patients may still be treated with regimens containing a cisplatin-based chemotherapy backbone. Currently ongoing clinical trials will help to better define patient populations optimized for each treatment.

Treatment options for advanced urothelial cancer after progression on chemotherapy and immune checkpoint inhibitors: a literature review.

OBJECTIVE: To describe the current treatment landscape in advanced urothelial cancer (aUC)/metastatic urothelial cancer and in particular to review the relevant literature highlighting recent advances in the treatment of patients with aUC after progression on chemotherapy and immune checkpoint inhibitor (ICI). BACKGROUND: aUC is a very aggressive disease with poor outcomes. Over the past several years, its treatment landscape has seen significant advances with the approval of ICI and targeted agents, which have led to improved outcomes. The current standard of care for most patients with aUC involves platinum-based chemotherapy followed by ICI after progression or as switch maintenance therapy (if no progression after chemotherapy). Treatment of patients following progression on ICI is more challenging, but novel therapies have been approved, such as erdafitinib for tumors with fibroblast growth factor receptor 2 (FGFR2) or FGFR3 activating mutation or fusion (can also be used following progression on platinum-based chemotherapy), enfortumab vedotin (EV) and sacituzumab govitecan (SG) in an unselected patient population. Many other trials in this space are currently ongoing and other promising agents may also potentially become available in the future. METHODS: Narrative overview of the recent literature relevant to the treatment of advanced/metastatic urothelial cancer following progression on chemotherapy and ICI was undertaken. Relevant literature was obtained from review of computerized databases including pubmed.gov and proceedings of major conferences including American Society of clinical Oncology (ASCO) Meetings, GU ASCO Symposia and European Society of Medical Oncology (ESMO) Meetings. CONCLUSIONS: In this narrative review, we highlight the current dynamic treatment landscape in aUC, emphasizing the recent important developments and a few examples of ongoing clinical trials. In particular, we focus on therapy options available following progression on platinum-based chemotherapy and ICI, a treatment space where until recently there had been no FDA-approved treatment options. The recent pivotal trials of antibody drug conjugates (ADCs) that led to FDA approvals in this space are highlighted, as are other agents currently in development. We conclude by discussing future directions and ongoing challenges in this evolving disease space.