FDA approves nivolumab plus cisplatin/gemcitabine in urothelial carcinoma

The FDA has approved nivolumab (Opdivo) in combination with frontline cisplatin and gemcitabine for the treatment of adult patients with unresectable or metastatic urothelial carcinoma.¹

In total, the open-label, randomized CheckMate-901 trial enrolled 608 adult patients with previously untreated unresectable or metastatic urothelial carcinoma.

The approval is based on data from the phase 3 CheckMate-901 trial (NCT03036098), which demonstrated improved overall survival (OS) and progression-free survival (PFS) with the nivolumab-combination therapy vs cisplatin/gemcitabine alone in this patient population.²

Specifically, at a median follow-up of 33 months, nivolumab in combination with cisplatin and gemcitabine followed by nivolumab maintenance therapy led to a 22% reduction in the risk of death, demonstrating a median OS of 21.7 months (95% CI, 18.6-26.4), vs 18.9 months (95% CI, 14.7-22.4) with cisplatin and gemcitabine alone (HR, 0.78; 95% CI, 0.63, 0.96; P = .0171).

Further, the median PFS with the nivolumab-combination therapy was 7.9 months (95% CI, 7.6-9.5), compared with 7.6 months (95% CI, 6.0-7.8) in the chemotherapy arm, translating to a 28% reduction in the risk of disease progression or death (HR, 0.72; 95% CI, 0.59, 0.88; P = .0012). At 12- and 24-month follow-up, PFS was 34.2% and 23.5%, respectively, among patients receiving the nivolumab-combination therapy, and 21.8% and 9.6%, respectively, among patients receiving cisplatin/gemcitabine alone.

The overall objective response rate (ORR) was 57.6% with nivolumab plus cisplatin/gemcitabine, with 21.7% of patients achieving a complete response (CR) and 35.9% achieving a partial response (PR). The ORR for patients receiving cisplatin/gemcitabine alone was 43.1%, with 11.8% of patients achieving a CR and 31.3% achieving a PR. The median duration of CR was 37.1 months in the treatment arm and 13.2 months in the control arm.

Regarding safety, 97% of patients in the nivolumab combination arm experienced any-grade treatment-related adverse events (TRAEs), compared with 93% of patients receiving cisplatin/gemcitabine alone. Further, 61.8% of patients receiving nivolumab plus cisplatin/gemcitabine experienced a grade 3 or higher adverse event (AE), compared with 51.7% of patients receiving cisplatin/gemcitabine alone. The most common AEs experienced in the nivolumab-combination therapy arm, occurring in 15% or more patients, were nausea, fatigue, musculoskeletal pain, constipation, decreased appetite, rash, vomiting, peripheral neuropathy, urinary tract infection, diarrhea, edema, hypothyroidism, and pruritus.

“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,” said Guru P. Sonpavde, MD, Medical Director of Genitourinary Oncology at the AdventHealth Cancer Institute in Orlando, Florida, in a news release.³ “Based on outcomes and the safety profile seen in the CheckMate-901 clinical trial, the approval of [nivolumab] 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.”

In total, the open-label, randomized CheckMate-901 trial enrolled 608 adult patients with previously untreated unresectable or metastatic urothelial carcinoma. Patients were randomly assigned 1:1 to receive either nivolumab plus cisplatin and gemcitabine for up to 6 cycles followed by nivolumab alone for up to 2 years, or to cisplatin and gemcitabine alone for up to 6 cycles.

The primary end points for the trial were OS and PFS as assessed by blinded independent central review using RECIST v1.1. Exploratory outcomes included objective response and safety.

Per the FDA, the recommended dosage for nivolumab is 360 mg every 3 weeks in combination with cisplatin and gemcitabine every 3 weeks for up to 6 cycles, followed by 240 mg every 2 weeks or 480 mg every 4 weeks as a monotherapy until disease progression, unacceptable toxicity, or up to 2 years.

References

1. FDA approves nivolumab in combination with cisplatin and gemcitabine for unresectable or metastatic urothelial carcinoma. News release. US Food and Drug Administration. March 6, 2024. Accessed March 7, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-nivolumab-combination-cisplatin-and-gemcitabine-unresectable-or-metastatic-urothelial

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

3. 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. News release. Bristol Myers Squibb. Published online and accessed March 7, 2024. https://www.businesswire.com/news/home/20240220135425/en/U.S.-Food-and-Drug-Administration-Approves-Opdivo%C2%AE-nivolumab-in-Combination-with-Cisplatin-and-Gemcitabine-for-First-Line-Treatment-of-Adult-Patients-with-Unresectable-or-Metastatic-Urothelial-Carcinoma