Dr Friedlander on Updates in Frontline Bladder Cancer Management

Terence W. Friedlander, MD, genitourinary oncologist, associate clinical professor, Division of Hematology/Oncology, Robert and Virginia O’Reilly Family Endowed Professor of Medicine, University of California San Francisco (UCSF), UCSF Health; chief, Hematology-Oncology, Zuckerberg San Francisco General; associate director, Cancer Research, Helen Diller Family Comprehensive Cancer Center, discusses updates in the frontline treatment of patients with bladder cancer.

There have been numerous exciting developments in bladder cancer management, both with approved therapies and promising agents still in the pipeline, Friedlander begins, stating that his approach to therapeutic sequencing forbladder cancer has evolved over the past few years. Traditionally, treatment options were centered around cisplatin-based chemotherapies, Friedlander explains. If patients were eligible, cisplatin was the go-to option, whereascarboplatin was used in those unable to tolerate cisplatin. However, pembrolizumab (Keytruda) has changed frontline bladder cancer management in the United States, particularly for frail patients who are entirely platinum ineligible, he notes.

In recent years, additional therapies have become available. For instance, taxanes and enfortumab vedotin-ejfv (Padcev) were introduced, along with the approval of FGFR inhibitors, Friedlander continues. The therapeutic arsenal for bladder cancer grew even further in 2021 when sacituzumab govitecan-hziy (Trodelvy) received accelerated FDA approval for the later-line treatment of patients with locally advanced or metastatic urothelial cancer.

More groundbreaking data came in the fall of 2023 when 2 significant phase 3 trials reported their findings in the metastatic setting, he emphasizes. The phase 3 CheckMate 901 trial (NCT03036098) demonstrated that adding nivolumab (Opdivo) to cisplatin-based chemotherapy resulted in a higher complete response rate and overall response rate in patients with previously untreated unresectable or metastatic disease, Friedlander expands. This trial solidified the combination of cisplatin and nivolumab as a beneficial treatment option in cisplatin-eligible patients, according to Friedlander.

At the same time, the phase 3 EV-302/KEYNOTE-A39 trial (NCT04223856) showed that combining enfortumab vedotin with pembrolizumab significantly improved overall survival, progression-free survival, and response rates compared with standard cisplatin or carboplatin-based chemotherapy in patients with first-line locally advanced or metastatic disease, he reports. Given these impressive results, enfortumab vedotin has become a dominant frontline therapy for metastatic bladder cancer, he says. However, for patients with contraindications like diabetes or peripheral neuropathy, platinum-based chemotherapy remains an option, Friedlander concludes.