Dr Guru Sonpavde: Nivolumab Plus Gemcitabine-Cisplatin Holds Promise in Urothelial Cancer

Urothelial carcinoma has long been treated with chemotherapy as the frontline standard of care, but recent trial results in the space have potential to add frontline immunotherapy to the treatment armamentarium and improve outcomes for the first time in decades.

One of those trials is the phase 3, multinational CheckMate 901 trial (NCT03036098), which found nivolumab plus gemcitabine-cisplatin to improve overall survival (OS) and progression-free survival (PFS) compared with gemcitabine-cisplatin chemotherapy alone in patients with advanced urothelial carcinoma.¹ The findings were published in The New England Journal of Medicine and presented at the 2023 European Society for Medical Oncology (ESMO) Congress.

CheckMate901 investigator Guru Sonpavde, MD, medical director of genitourinary oncology, assistant director of the clinical research unit, and Christopher K. Glanz Chair for Bladder Cancer Research at the AdventHealth Cancer Institute, discussed the trial’s findings in an interview with The American Journal of Managed Care^® (AJMC^®).

Sonpavde Discusses the Rationale Behind CheckMate 901

In the CheckMate 901 study, a total of 608 patients were randomized to receive either the nivolumab combination or gemcitabine-cisplatin alone. OS was longer in the combination therapy group at a median follow-up of 33.6 months (HR for death, 0.78; 95% CI, 0.63-0.96; P = .02), with median survival of 21.7 months (95% CI, 18.6-26.4) and 18.9 months (95% CI, 14.7-22.4), respectively.

PFS was also improved in the combination therapy group vs chemotherapy alone (HR for progression or death, 0.72; 95% CI, 0.59-0.88; P = .001). At 12 months, PFS was 34.2% in the nivolumab plus chemotherapy group, compared with 21.8% in the chemotherapy alone group.

Overall, 57.6% of patients experienced an objective response in the nivolumab combination group vs 43.1% in the gemcitabine-cisplatin group. Furthermore, 21.7% of patients showed complete responses (CRs) in the combination therapy group, and those responses were notably durable with a median of 37.1 months. In the chemotherapy alone group, 11.8% of patients experience CR, and the median duration was 13.2 months.

Comparing Nivolumab Plus Chemotherapy With the Standard of Care

Sonpavde noted that there have been other positive findings in advanced urothelial cancer recently with potential to change the firstline standard of care. Specifically, enfortumab vedotin (EV) plus pembrolizumab demonstrated promising outcomes in the phase 3 EV-302/KEYNOTE-A39 trial, which was also presented at ESMO 2023.²

The progress seen in the space in recent months is unprecedented, as chemotherapy has been the standard of care for decades. But in this dynamic landscape, the glaring question is how to choose between regimens. Sonpavde shared his insight on where nivolumab plus gemcitabine-cisplatin may fit into the urothelial carcinoma treatment algorithm given the findings around EV plus pembrolizumab, which showed impressive OS and PFS improvements vs standard-of-care chemotherapy.

Treatment Considerations in the Changing Urothelial Carcinoma Landscape

While any course of treatment carries pros and cons, Sonpavde highlighted certain aspects of the nivolumab regimen, such as its limited chemotherapy cycles, affordability, and overall accessibility, that warrant consideration in treatment decisions. He also noted that with both nivolumab plus chemotherapy and EV plus pembrolizumab potentially on the table, the JAVELIN paradigm of upfront chemotherapy and maintenance immunotherapy may be relegated to select patients.

Sonpavde also discussed key findings of the CheckMate 901 trial in a video interview with AJMC.

References

1. van der Heijden MS, Sonpavde G, Powles T, et al. Nivolumab plus gemcitabine-cisplatin in advanced urothelial carcinoma. N Engl J Med. 2023;389(19):1778-1789. doi:10.1056/NEJMoa2309863

2. Joszt L. First in decades: enfortumab vedotin + pembrolizumab beats chemo in first-line metastatic urothelial cancer. AJMC. October 22, 2023. Accessed November 30, 2023. https://www.ajmc.com/view/first-in-decades-enfortumab-vedotin-pembrolizumab-beats-chemo-in-first-line-metastatic-urothelial-cancer