Nivolumab plus chemotherapy nears EU approval for urothelial carcinoma

The European Medical Agency’s (EMA’s) Committee for Medicinal Products for Human Use (CHMP) has issued a positive opinion recommending approval of nivolumab (Opdivo) in combination with cisplatin and gemcitabine for the front-line treatment of patients with unresectable or metastatic urothelial carcinoma.¹

The recommendation by the CHMP is supported by findings from a sub-study of the phase 3 CheckMate-901 study.

According to a news release from Bristol Myers Squibb,1 approval of this combination would mark the first immunotherapy-chemotherapy regimen approved in the European Union (EU) for this patient population.

“For eligible patients with unresectable or metastatic urothelial carcinoma, platinum-based chemotherapy in the first-line setting has been the standard of care for decades, but the durability of response to chemotherapy alone is poor and once a patient progresses, treatment options become increasingly limited,” said Dana Walker, vice president and Global Program Lead, Genitourinary Cancers, Bristol Myers Squibb, in the news release.¹ “New treatment options that may improve responses, delay disease progression, and offer survival benefit in the first-line setting are needed. With today’s CHMP positive opinion, we are one step closer to potentially providing eligible patients with unresectable or metastatic urothelial carcinoma in the European Union with a new first-line treatment option.”

A decision regarding EU marketing authorization is expected by June 2024.

Nivolumab was also granted FDA approval in March 2024 for use in combination with cisplatin/gemcitabine in the treatment of patients with unresectable or metastatic urothelial carcinoma.²

Both the FDA approval and the current recommendation by the CHMP were supported by findings from a sub-study of the phase 3 CheckMate-901 study (NCT03036098), which demonstrated that nivolumab plus cisplatin/gemcitabine followed by nivolumab monotherapy prolonged overall survival (OS) and progression-free survival (PFS) in patients with unresectable or metastatic urothelial carcinoma vs cisplatin/gemcitabine alone. Findings from the study were presented at the 2023 European Society of Medical Oncology Congress in Madrid, Spain and published in the New England Journal of Medicine.³

At a median follow-up of approximately 33 months, patients who received the nivolumab regimen demonstrated a median OS of 21.7 months, compared with 18.9 months among those receiving chemotherapy alone (HR, 0.78; 95% CI, 0.63, 0.96; P = .0171). At the 12-month landmark analysis, the OS rate for the nivolumab regimen was 70.2%, compared with 62.7% compared with chemotherapy. At 24-month landmark analysis, the OS rate was 46.9% in the nivolumab arm, compared with 40.7% in the chemotherapy arm.

Further, treatment with nivolumab reduced the risk of progression or death by 28%, with a median PFS of 7.9 months vs 7.6 months with chemotherapy alone (HR, 0.72; 95% CI. 0.59, 0.88; P = .0012). At the 12-month landmark analysis, PFS was 34.2% among patients who received the nivolumab regimen vs 21.8% among those who received chemotherapy alone. At the 24-month analysis, PFS was 23.5% in the nivolumab cohort compared with 9.6% in the chemotherapy alone cohort.

In total, the sub-study of the phase 3 CheckMate-901 trial included 608 adult patients with unresectable or metastatic urothelial carcinoma. Patients were randomly assigned to receive 360 mg nivolumab in combination with cisplatin/gemcitabine every 3 weeks for up to 6 cycles followed by 480 mg nivolumab monotherapy every 4 weeks for up to 2 years or until disease progression or death, or to cisplatin/gemcitabine alone every 3 weeks for up to 6 cycles. The primary end points for the trial were OS and PFS.

The primary open-label, phase 3 CheckMate-901 study sought to evaluate nivolumab in combination with ipilimumab (Yervoy) or nivolumab in combination with cisplatin/gemcitabine following by nivolumab monotherapy vs cisplatin/gemcitabine alone in patients with previously untreated unresectable or metastatic urothelial carcinoma.

The primary CheckMate-901 study remains ongoing to assess nivolumab plus ipilimumab vs standard-of-care chemotherapy.

References

1. CHMP adopts positive opinion recommending approval of Bristol Myers Squibb’s Opdivo (nivolumab) in combination with cisplatin and gemcitabine for the first-line treatment of adult patients with unresectable or metastatic urothelial carcinoma. News release. Bristol Myers Squibb. Published online and accessed April 26, 2024. https://news.bms.com/news/corporate-financial/2024/CHMP-Adopts-Positive-Opinion-Recommending-Approval-of-Bristol-Myers-Squibbs-Opdivo-nivolumab-in-Combination-with-Cisplatin-and-Gemcitabine-for-the-First-Line-Treatment-of-Adult-Patients-with-Unresectable-or-Metastatic-Urothelial-Carcinoma/default.aspx

2. 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 April 26, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-nivolumab-combination-cisplatin-and-gemcitabine-unresectable-or-metastatic-urothelial

3. 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