FDA Approves Nivolumab Plus Platinum-Doublet Chemo for Unresectable or Metastatic Urothelial Carcinoma

The FDA approved nivolumab (Opdivo) in combination with cisplatin and gemcitabine as first-line treatment of adult patients with unresectable or metastatic urothelial carcinoma.

This approval was based on findings from the CheckMate-901 (NCT03036098) trial, according to an alert from the FDA. In this randomized, open-label trial, researchers analyzed data from 608 patients with previously untreated unresectable or metastatic urothelial carcinoma. Patients were randomized 1:1 to receive either nivolumab with cisplatin and gemcitabine for up to 6 cycles followed by nivolumab alone for up to 2 years, or cisplatin and gemcitabine for up to 6 cycles. Patients from both groups who discontinued cisplatin were allowed to receive carboplatin. Of note, for randomization, patients were stratified by tumor PD-L1 expression and the presence of liver metastasis.

The major efficacy outcome measures of the CheckMate-901 trial were overall survival (OS) and progression-free survival (PFS), assessed by blinded independent central review with RECIST v1.1, according to the alert.

Patients assigned nivolumab with cisplatin and gemcitabine had statistically significant benefits in OS and PFS compared to those assigned cisplatin and gemcitabine alone. The median OS was 21.7 months (95% CI, 18.6-26.4) in the nivolumab plus cisplatin and gemcitabine group compared with 18.9 months (95% CI, 14.7-22.4) in the cisplatin and gemcitabine group (HR = 0.78; 95% CI, 0.63-0.96; 2-sided P = .0171). The median PFS was 7.9 months (95% CI, 7.6-9.5) in the nivolumab combination group vs 7.6 months (95% CI, 6.0-7.8) in the cisplatin plus gemcitabine group (HR = 0.72; 95% CI, 0.59-0.88; 2-sided P = .0012).

The most common adverse reactions, occurring in at least 15% of patients treated with nivolumab plus platinum-doublet chemotherapy in the trial, included fatigue, nausea, constipation, musculoskeletal pain, rash, decreased appetite, vomiting, urinary tract infection, peripheral neuropathy, edema, diarrhea, pruritis, and hypothyroidism, according to the alert.

The recommended dose of nivolumab for this specific indication is 360 mg every 3 weeks in combination with cisplatin and gemcitabine every 3 weeks for up to 6 cycles, followed by 240 mg of nivolumab every 2 weeks for 480 mg every 4 weeks as a single agent until unacceptable toxicity, disease progression, or a maximum treatment of 2 years from the first dose.

The supplemental biologics license application for nivolumab plus cisplatin-based chemotherapy for frontline treatment of adult patients with unresectable or metastatic urothelial carcinoma was granted priority review in December 2023.

Reference

FDA approves nivolumab in combination with cisplatin and gemcitabine for unresectable or metastatic urothelial carcinoma. News release. FDA. March 7, 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