FDA Approves Nivolumab Plus Chemotherapy for Unresectable or Metastatic Urothelial Carcinoma


A clinical trial showed that nivolumab plus chemotherapy significantly improved overall survival and progression-free survival compared with a chemotherapy combination alone.

The FDA has approved the first concurrent immunotherapy-chemotherapy combination for the first-line treatment of adults with unresectable or metastatic urothelial carcinoma.1 The approval of the PD-1 inhibitor nivolumab (Opdivo) with cisplatin and gemcitabine was based on the results of the phase 3 CheckMate 901 trial (NCT03036098).

FDA headquarters / Tada Images - stock.adobe.com

FDA headquarters / Tada Images - stock.adobe.com

The trial showed the combination significantly improved overall survival (OS) and progression-free survival (PFS) compared with the chemotherapy combination alone. The approval comes amid the ongoing cisplatin shortage.

Key Takeaways

  • Nivolumab plus cisplatin and gemcitabine has been approved by the FDA as a first-line treatment for untreated metastatic urothelial carcinoma.
  • This is the first FDA-approved immunotherapy-chemotherapy combination for this condition.
  • A phase 3 trial showed that the new treatment improved overall and progression-free survival compared to standard chemotherapy.

“This approval marks an important advancement in a historically difficult-to-treat setting, where there has been a need for new and differentiated first-line approaches that may offer patients a chance to live longer,” Guru P. Sonpavde, MD, medical director of genitourinary oncology and the phase 1 clinical research unit and the Christopher K. Glanz Chair for Bladder Cancer Research at the AdventHealth Cancer Institute, Orlando, Florida, said in a statement.1 “Based on outcomes and the safety profile seen in the CheckMate-901 clinical trial, the approval of Opdivo in combination with cisplatin and gemcitabine has the potential to change how metastatic or unresectable [urothelial carcinoma] is treated for certain patients and offers them new hope.”

Nivolumab was already approved in urothelial carcinoma as an adjuvant treatment for adults who are at high risk of recurrence after radical resection and for adults with locally advanced or metastatic urothelial carcinoma who had disease progression during or after receiving platinum-containing chemotherapy or who had disease progression within 12 months of receiving neoadjuvant or adjuvant platinum-containing chemotherapy.

CheckMate 901

In the phase 3 trial,2 608 patients were assigned in a randomized fashion to receive either the nivolumab combination or the chemotherapy combination alone. The group receiving the nivolumab combination had a median survival of 21.7 (95% CI, 18.6-26.4) months at the median follow-up of 33.6 months compared with 18.9 (95% CI, 14.7-22.4) months for the chemotherapy group, reducing the risk of death by 22% (HR 0.78; 95% CI: 0.63-0.96; P = .0171).

The risk of disease progression or death was reduced by 28% for patients receiving the nivolumab combination with a median PFS of 7.9 months vs 7.6 months for chemotherapy alone (HR 0.72; 95% CI: 0.59-0.88; P = .0012).

The most frequent serious adverse events (AEs) in patients receiving the nivolumab combination were urinary tract infection (4.9%), acute kidney injury (4.3%), anemia (3.0%), pulmonary embolism (2.6%), sepsis (2.3%), and platelet count decreased (2.3%). The most common AEs were nausea, fatigue, musculoskeletal pain, constipation, decreased appetite, rash, vomiting, and peripheral neuropathy.

Urothelial Cancer

Urothelial carcinoma accounts for 90% of bladder cancers, and bladder cancer is the sixth most common cancer in the US.3 Up to 25% of patients present with metastatic disease and have limited treatment options.4,5

This is the second recent approval metastatic urothelial carcinoma. For decades, the standard of care in the first line for patients with locally advanced or metastatic urothelial carcinoma was chemotherapy. However, this was recently challenged with the results of EV-302/KEYNOTE-A39, presented at ESMO Congress 2023, which found enfortumab vedotin, an antibody drug conjugate, plus the PD-1 inhibitor pembrolizumab significantly improved the outcomes for patients by nearly doubling the PFS and OS.6

Enfortumab vedotin plus pembrolizumab was approved by the FDA December 18, 2023.7 The approval was based on the findings of the EV-302/KEYNOTE-A39 trial.

READ MORE: Oncology Resource Center

This article originally appeared in AJMC.

1. US Food and Drug Administration approves Opdivo (nivolumab), in combination with cisplatin and gemcitabine, for first-line treatment of adults patients with unresectable or metastatic urothelial carcinoma. New release. Bristol Myers Squibb. March 7, 2024. Accessed March 7, 2024. https://news.bms.com/news/corporate-financial/2024/U.S.-Food-and-Drug-Administration-Approves-Opdivo--nivolumab-in-Combination-with-Cisplatin-and-Gemcitabine-for-First-Line-Treatment-of-Adult-Patients-with-Unresectable-or-Metastatic-Urothelial-Carcinoma/default.aspx
2. van der Heijden MS, Sonpavde G, Powles T, et al; CheckMate 901 Trial Investigators. N Engl J Med. 2023;389(19):1778-1789. doi:10.1056/NEJMoa2309863
3. Urothelial carcinoma (transitional carcinoma). Cleveland Clinic. Reviewed January 1, 2023. Accessed March 7, 2024. https://my.clevelandclinic.org/health/diseases/6239-transitional-cell-cancer
4. Svatek RS, Siefker-Radtke A, Dinney CP. Management of metastatic urothelial cancer: the role of surgery as an adjunct to chemotherapy. Can Urol Assoc J. 2009;3(6 Suppl 4):S228-S231. doi:10.5489/cuaj.1203
5. Vassiliou V, Katsila T, Sodergren SC, Kardamakis D. Radiotherapy in metastatic urothelial carcinoma: rationale and clinical applications. Anticancer Res. 2022;42(8):3767-3778. doi:10.21873/anticanres.15867
6. Joszt L. First in decades: enfortumab vedotin + pembrolizumab beats chemo in first-line metastatic urothelial cancer. The American Journal of Managed Care® website. October 22, 2023. Accessed March 7, 2024. https://www.ajmc.com/view/first-in-decades-enfortumab-vedotin-pembrolizumab-beats-chemo-in-first-line-metastatic-urothelial-cancer
7. McNulty R. FDA approves enfortumab vedotin plus pembrolizumab for locally advanced or metastatic bladder cancer. The American Journal of Managed Care website. December 18, 2023. Accessed March 7, 2024. https://www.ajmc.com/view/fda-approves-enfortumab-vedotin-plus-pembrolizumab-for-locally-advanced-or-metastatic-bladder-cancer
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