Nivolumab/Chemotherapy Leads to OS, PFS Improvements in UC

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A treatment regimen of nivolumab (Opdivo) and cisplatin-based chemotherapy followed by nivolumab monotherapy demonstrated clinically meaningful and statistically significant improvements in overall survival (OS) and progression-free survival (PFS) compared with the standard of care (SoC) cisplatin-based therapy for patients with cisplatin-eligible unresectable or metastatic urothelial carcinoma (UC), according to findings from the CheckMate-901 trial (NCT03036098).¹

"This trial demonstrates that gemcitabine, cisplatin, plus nivolumab significantly improved [PFS] and [OS] vs gemcitabine plus cisplatin. This is a major finding because other trials comparing platinum-based chemotherapy plus immune checkpoint blockade in metastatic urothelial cancer have not demonstrated a survival benefit," said Matthew Galsky, MD, professor of medicine (hematology and medical oncology), director of Genitourinary Medical Oncology, co-director of the Center of Excellence for Bladder Cancer at the Tisch Cancer Institute, and CheckMate-901 principal investigator.

“This survival benefit seen with nivolumab in combination with cisplatin-based chemotherapy represents a momentous accomplishment that may provide hope for patients [with UC] as the first concurrent chemo-immunotherapy combination to demonstrate such an improvement compared to [SoC] cisplatin-based combinations. The implications of these data have the potential to be practice-changing and transform the way cisplatin-eligible patients are treated,” said Michiel S. van der Hejiden, MD, PhD, Department of Medical Oncology, Netherlands Cancer Institute, in a press release.

With a median follow-up of approximately 33 months, the risk of death in the treatment arm was reduced by 22%. The median OS in the treatment arm was 21.7 months compared with 18.9 months in the active comparator arm that received chemotherapy alone (hazard ratio [HR] 0.78; 95% CI, 0.63-0.96; P =.0171). At the 12- and 24-month landmarks, the OS rates in the treatment arm were 70.2% and 46.9%, respectively, compared with 62.7% and 40.7% in the active comparator arm.

The risk of death or disease progression in the treatment arm was reduced by 28%; the median PFS was 7.9 months compared with 7.6 months in the active comparator arm (HR 0.72; CI 0.59-0.88; P =.0012). At the 12- and 24-month landmarks, PFS rates were 34.2% and 23.5% in the treatment arm, respectively, compared with 21.8% and 9.6% in the active comparator arm.

A 15%-higher objective response rate was observed in the treatment arm compared with the active comparator arm (57.6% vs 43.1%). There was a near doubling of patients who achieved a complete response (CR) in the treatment arm compared with the active comparator arm (21.7% vs 11.8%). The median CR duration was also nearly tripled in the treatment arm compared with the active comparator arm (37.1 months vs 13.2 months).

Regarding safety, investigators noted a tolerable safety profile consistent with the known profiles of the individual regimen agents. No new safety concerns were observed.¹

A total of 1290 participants were enrolled, and 608 cisplatin-eligible patients were randomized to receive 360 mg of nivolumab and cisplatin-based chemotherapy or chemotherapy alone every 3 weeks, followed by 480 mg of nivolumab every 4 weeks until disease progression or death for up to 2 years.

The study’s primary end points are 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 are 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.

To be eligible for the trial, patients needed to have histological or cytological evidence of metastatic or surgically inoperable transitional cell cancer of the urothelium, not received prior chemotherapy, and an ECOG performance status of 0 or 1. Women and men must also have agreed to follow specific methods of contraception. Patients were not eligible for the trial if they had disease that was suitable for local therapy, a serious uncontrolled medical disorder, or prior treatment with an anti PD-1, anti PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA4 antibody.²

These data will be featured in a presidential symposium during the European Society of Medical Oncology Congress 2023 on October 22, 2023.¹

REFERENCES:

1. Opdivo (nivolumab) in combination with cisplatin-based chemotherapy followed by opdivo demonstrates significant survival benefits for cisplatin-eligible patients with unresectable or metastatic urothelial carcinoma in phase 3 CheckMate-901 trial. News release. Bristol Myers Squibb. October 17, 2023. Accessed October 18, 2023. https://tinyurl.com/7ppr3jyk

2. Study of nivolumab in combination with ipilimumab or standard of care chemotherapy compared to standard of care chemotherapy alone in treatment of participants with untreated inoperable or metastatic urothelial cancer (CheckMate901). ClinicalTrials.gov. Updated October 12, 2023. Accessed October 18, 2023. https://clinicaltrials.gov/study/NCT03036098