Nivolumab Plus Cisplatin and Gemcitabine Approved for Unresectable or Metastatic Urothelial Carcinoma

Ulka Vaishampayan, MD, MBBS.

The FDA has granted approval to nivolumab (Opdivo®, Bristol Myers Squibb Company) in combination with cisplatin and gemcitabine for the first-line treatment of adult patients with unresectable or metastatic urothelial carcinoma (UC). 

What they studied: Efficacy was studied in the phase 3, open-label CheckMate 901 trial (NCT03036098), on which approval was based, in which 608 patients with previously untreated unresectable or metastatic UC were enrolled. Patients were randomized 1:1 to receive either nivolumab plus cisplatin and gemcitabine for up to 6 cycles, followed by nivolumab alone for up to two years, or cisplatin and gemcitabine alone for up to 6 cycles. Randomization was stratified by programmed cell death ligand 1 (PD-L1) expression and presence of liver metastasis. Patients discontinuing cisplatin were permitted to receive carboplatin in either arm.

The major primary end points measured were overall survival and progression-free survival as assessed by blinded independent central review using RECIST v1.1.

What they found: The trial produced statistically significant improvements for both overall survival and progression-free survival in those receiving nivolumab plus cisplatin and gemcitabine. The median overall survival was 21.7 months for patients in the nivolumab arm compared with 18.9 months for those receiving cisplatin and gemcitabine alone. Progression-free survival was seen at a median of 7.9 months in the nivolumab arm compared with 7.6 months in those receiving cisplatin and gemcitabine alone.

Additional efficacy results: The overall response rate with the nivolumab combination was 57.1%, with 21.6% of patients achieving a complete response, including a prolonged 37.1-month median duration of complete response. For those receiving the combination treatment, progression-free survival was 23.5% at two years compared with 9.5% in those receiving cisplatin and gemcitabine alone.

Adverse events: The rate of severe toxicities was 61.7% in the nivolumab arm compared with 51.7% in the chemotherapy-alone arm. The most common adverse events experienced by ≥15% of patients receiving nivolumab with platinum-doublet chemotherapy were nausea, fatigue, musculoskeletal pain, constipation, decreased appetite, rash, vomiting, peripheral neuropathy, urinary tract infection, diarrhea, edema, hypothyroidism, and pruritis. 

Conclusion: “The regimen is overall well-tolerated and enables patients and oncologists to limit the duration and toxicities of chemotherapy,” concluded Dr. Vaishampayan. “This regimen has created new hope towards improving outcomes and limiting toxicity for UC patients.”

Instructions: The recommended dosage of nivolumab for this indication is as follows: 360 mg of nivolumab plus cisplatin and gemcitabine every three weeks for up to six cycles, followed by 240 mg of nivolumab every two weeks, or 480 mg every four weeks, as a single agent for a maximum treatment of two years from first dose, or until disease progression or unacceptable toxicity.

For More Information

van der Heijden MS, Sonpavde G, Powles T, et al (2023). Nivolumab plus gemcitabine-cisplatin in advanced urothelial carcinoma. N Engl J Med, 389(19):1778-1789. DOI:10.1056/NEJMoa2309863 (2024). Study of nivolumab in combination with ipilimumab or standard of care chemotherapy compared to the standard of care chemotherapy alone in treatment of participants with untreated inoperable or metastatic urothelial cancer (CheckMate901). NLM identifier: NCT03036098.

Opdivo® (nivolumab) prescribing information (2024). Bristol Myers Squibb Company. Available at:

US Food and Drug Administration (2024). FDA approves nivolumab in combination with cisplatin and gemcitabine for unresectable or metastatic urothelial carcinoma. Available at:

Image credit: CoRus13. Licensed under CC0 1.0

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