Editorial Comment to Combination therapy with paclitaxel and gemcitabine after platinum‐based chemotherapy in patients with advanced urothelial cancer

Abstract

The medical treatment paradigm for advanced urothelial cancer (UC) has been changing dramatically since the introduction of immune checkpoint inhibitors. Currently, the gemcitabine/cisplatin regimen and pembrolizumab is widely used as standard first-line and second-line therapy, respectively. To improve treatment outcomes, various clinical trials that use a combination of immune checkpoint inhibitors and other agents are currently ongoing. The medical treatment and standard regimen for advanced UC is developing and changing year-by-year. There are, and there will continue to be, however, patients who have a good performance status following progression after standard therapy. These patients often undergo cytotoxic chemotherapies. In this issue of International Journal of Urology, Harada et al. reported the efficacy and tolerability of paclitaxel and gemcitabine therapy after platinum-based chemotherapy for patients with advanced UC. The paclitaxel and gemcitabine therapy was active and tolerable, achieving a 29% objective response rate and an 11.5-month overall survival period in patients with platinum-refractory advanced UC. In terms of adverse events, myelosuppression was the most common. Among non-hematological toxicities, peripheral sensory neuropathy, arthralgia and hepatic damage were widely observed, and most adverse events were manageable. Enfortumab vedotin is a novel designated antibody-drug conjugate anticancer agent. Due to the excellent results of the global phase III trial, EV-301, enfortumab vedotin will be the recommended third-line regimen for the treatment of advanced UC patients who previously received both platinum-containing and immune checkpoint inhibitor therapies. High response rates to enfortumab vedotin in combination with pembrolizumab as the first-line treatment for metastatic disease was reported. Consequently, the current global phase III EV-302 clinical trial, which investigates the possibility of the combination of enfortumab vedotin and pembrolizumab as first-line therapy, is ongoing. Nevertheless, cytotoxic chemotherapy remains important because, as described above, some patients (present and future) will achieve good performance status after receiving the current standard therapy. As these patients often undergo cytotoxic chemotherapies, information on cytotoxic chemotherapy, particularly, that related to adverse events, is meaningful.