CHMP Recommends Frontline Nivolumab Plus Chemo in Unresectable/Metastatic Urothelial Carcinoma

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended the approval of nivolumab (Opdivo) plus cisplatin and gemcitabine for the frontline treatment of adult patients with unresectable or metastatic urothelial carcinoma. The final decision from the European Commission is expected in June 2024.¹

The recommendation was based on findings from the phase 3 CheckMate-901 trial (NCT03036098), which evaluated nivolumab in combination with cisplatin and gemcitabine followed by nivolumab monotherapy (n = 304) vs cisplatin and gemcitabine alone (n = 304).

Findings from the study, which were presented during the 2023 ESMO Congress and subsequently published in The New England Journal of Medicine, demonstrated that patients on the nivolumab and chemotherapy arm achieved a median overall survival (OS) of 21.7 months (95% CI, 18.6-26.4) compared with 18.9 months (95% CI, 14.7-22.4) in the chemotherapy alone arm (HR, 0.78; 95% CI, 0.63-0.96; P = .02). Moreover, the median progression-free survival (PFS) was 7.9 months (95% CI, 7.6-9.5) vs 7.6 months (95% CI, 6.1-7.8), respectively (HR, 0.72; 95% CI, 0.59-0.88; P = .001), and the 12-month PFS rates were 34.2% (95% CI, 28.6%-40.0%) vs 21.8% (95% CI, 16.1%-27.9%), respectively.²

“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,” Dana Walker, MD, MSCE, vice president and global program lead, Genitourinary Cancers, Bristol Myers Squibb, said in a press 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.”

Notably, the FDA recently approved nivolumab plus cisplatin and gemcitabine for the frontline treatment of adult patients with unresectable or metastatic urothelial carcinoma on March 7, 2024; this approval was also based on findings from CheckMate-901.³

CheckMate-901 was an international, open-label study that randomly assigned patients with previously untreated, unresectable or metastatic urothelial carcinoma 1:1 to receive intravenous nivolumab at 360 mg plus gemcitabine and cisplatin every 3 weeks for up to 6 cycles followed by nivolumab at 480 mg every 4 weeks for up to 2 years or gemcitabine and cisplatin alone every 3 weeks for up to 6 cycles. Eligible patients must be at least 18 years old, have measurable disease per RECIST 1.1, and have an ECOG performance status of 1 or less.²

The coprimary end points were OS and PFS. Secondary end points included OS and PFS in patients with PD-L1 expression of 1% or more and health-related quality of life. Objective response rate and safety were exploratory end points.

In terms of safety, patients in the investigational (n = 304) and control (n = 288) safety populations experienced an any-grade adverse effect (AE) at a rate of 97.4% vs 92.7%, respectively. Grade 3 or higher AEs were reported at a rate of 61.8% vs 51.7%, respectively. Any-grade treatment-related AEs leading to treatment discontinuation (21.1% vs 17.4%) and grade 3 or higher events leading to discontinuation (11.2% vs 7.6%) were present in both arms.

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. April 26, 2024. 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. van der Heijden MS, Sonpavde G, Powles T, et al. Nivolumab plus gemcitabine-cisplatin in advanced urothelial carcinoma. N Engl J Med. 2023;389(19):1778-1789. doi:10.1056/NEJMoa2309863
3. FDA approves nivolumab in combination with cisplatin and gemcitabine for unresectable or metastatic urothelial carcinoma. FDA. 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