Nivolumab With Chemotherapy Gains FDA Approval in Urothelial Cancer


Nivolumab given with cisplatin-based chemotherapy has received approval from the FDA for patients with treatment-naive unresectable or mUC.

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  • The FDA has approved nivolumab (Opdivo) plus cisplatin-based chemotherapy for the first-line treatment of patients with previously untreated unresectable or metastatic urothelial carcinoma (mUC).
  • Findings from the phase 3 CheckMate -901 study (NCT03036098) support this approval.
  • The addition of nivolumab to chemotherapy resulted in higher objective response rates (ORR), including a greater proportion of complete responses (CR), and a longer median duration of response (DOR) compared with chemotherapy alone.

Nivolumab plus cisplatin-based chemotherapy has been approved by the FDA for the treatment of patients with treatment-naive unresectable or mUC.1

This regulatory decision is supported by results from the phase 3 CheckMate-901 study in which findings were published in the New England Journal of Medicine and presented at the 2023 European Society for Medical Oncology Annual Congress. Here, the combination led to improvements in overall survival (OS; HR, 0.78; 95% CI, 0.63-0.96; P =.02) and progression-free survival (PFS; HR, 0.72; 95% CI, 0.59-0.88; P =.001) compared with gemcitabine/cisplatin alone.

At a median follow-up of approximately 33 months, nivolumab plus cisplatin-based chemotherapy produced a median OS of 21.7 months (95% CI, 18.6-26.4) vs 18.9 months (95% CI, 15.7-22.4) with chemotherapy.2At 12 and 24 months, the OS rates in the nivolumab combination arm were 70.2% and 46.9%, respectively, compared with 62.7% and 40.7% in the active comparator arm.

PFS was 34.2% in the combination arm vs 21.8% in the chemotherapy arm at 12 months, 23.5% and 9.6% at 24 months, and the median PFS was 7.9 months vs 7.6 months, respectively, (HR 0.72; CI 0.59-0.88; P =.0012). The ORR was 57.6% with the nivolumab combination arm and 43.1% with chemotherapy alone. Further, the CR rate in the nivolumab combination arm was 21.7% vs 11.8% with chemotherapy alone, and the median DOR was 37.1 months vs 13.2, respectively.

Grade 3 or higher adverse events were observed in 61.8% of patients in the nivolumab combination arm and 51.7% in the chemotherapy arm; however, no new safety concerns were identified.2,3

Illustration of bladder cancer: ©vitanovski -

Illustration of bladder cancer: ©vitanovski -

The phase 3, open-label study randomized 608 patients who received either nivolumab in combination with ipilimumab (Yervoy) or cisplatin-based chemotherapy followed by nivolumab monotherapy or standard-of-care chemotherapy alone.1,2

To be considered eligible for enrollment, patients need to have histological or cytological evidence of metastatic or inoperable UC, not receive any prior systemic chemotherapy for UC, have an ECOG performance status of 0 to 1, and follow specific methods of contraception, if applicable. Patients were not eligible to enroll if they had disease that was suitable for local therapy, any uncontrolled medical disorder, or had received prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody.3,4

Finally, the primary end points of the study were OS in cisplatin-ineligible patients, OS in PD-L1-positive patients, PFS in cisplatin-eligible patients with previously untreated UC, and OS in cisplatin-eligible patients with previously untreated UC. The secondary end points were PFS in cisplatin-ineligible patients, PFS in PD-L1-positive patients, PFS in all patients, EORTC Global Health Status score, EORTC Global Health Status score in cisplatin-eligible and previously untreated UC, PFS by PD-L1 expression, and OS by PD-L1 expression.

1. FDA approves nivolumab in combination with cisplatin and gemcitabine for unresectable or metastatic urothelial carcinoma. U.S. FDA. March 6, 2024. Accessed March 7, 2024.
2. U.S. Food and Drug Administration accepts for priority review Bristol Myers Squibb’s application for Opdivo (nivolumab) in combination with cisplatin-based chemotherapy for first-line treatment of adult patients with unresectable or metastatic urothelial carcinoma. News release. Bristol Myers Squibb. December 5, 2023. Accessed December 5, 2023.
3. Van der Heijden M, Sonpavde G, Powles T, et al. Nivolumab plus gemcitabine-cisplatin in advanced urothelial carcinoma. November 9, 2023. N Engl J Med. 2023;389(19):1778-1789. doi:10.1056/NEJMoa2309863
4. 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 carcinoma (CheckMate901). Updated November 30, 2023. Accessed December 5, 2023.
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