Adjuvant nivolumab could become the standard of care for patients with metastatic bladder cancer, according to data presented at the American Urological Association (AUA) 2022 Annual Meeting.¹

With longer follow-up, the results of the phase III CheckMate 274 trial showed that treatment with the anti–PD-1 therapy nivolumab continued to demonstrate a clinically meaningful improvement in disease-free survival vs placebo for patients with high-risk muscle-invasive urothelial cancer after radical surgery, both in the intent-to-treat population and in the subset of patients with PD-L1 expression of at least 1%. Authors of the study also reported benefits in secondary and exploratory endpoints, including non–urothelial tract recurrence–free survival and distant metastasis–free survival.

“Longer-term follow-up data are important for reinforcing the initial results we published this past year, demonstrating for the first time that immunotherapy administered after surgery for bladder cancer and other urothelial cancer can decrease the risk of cancer recurrence,” said lead study author Matthew Galsky, MD, Director of Genitourinary Medical Oncology and Co-Director of the Center of Excellence for Bladder Cancer at The Tisch Cancer Institute, Mount Sinai Health System, New York. “Almost 200,000 people die each year of urothelial cancer worldwide, so advances like immunotherapy being used in this manner bring hope.”

These results support adjuvant nivolumab as a standard-of-care treatment for patients with muscle-invasive urothelial cancer at high risk for recurrence after radical surgery.

— Matthew Galsky, MD

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“These results support adjuvant nivolumab as a standard-of-care treatment for patients with muscle-invasive urothelial cancer at high risk for recurrence after radical surgery,” he added.

As Dr. Galsky explained, the standard of care for muscle-invasive urothelial carcinoma is surgery with or without cisplatin-based neoadjuvant chemotherapy, but most patients with this disease still experience recurrence. There is currently no evidence supporting the use of adjuvant chemotherapy after neoadjuvant chemotherapy, he added, and limited data to support the use of adjuvant cisplatin-based chemotherapy in patients who have not received neoadjuvant chemotherapy (except for those with upper tract disease). Furthermore, many patients are not eligible or willing to receive chemotherapy.

Study Methods

In the randomized, phase III, double-blind, multicenter CheckMate 274 trial, with a minimum follow-up of 5.9 months in the intent-to treat population, adjuvant nivolumab provided a significant disease-free survival benefit vs placebo in patients with high-risk muscle-invasive urothelial carcinoma after radical surgery. Investigators randomly assigned 709 patients to receive nivolumab (240 mg intravenously every 2 weeks for up to 1 year) vs placebo, and randomization was stratified by PD-L1 expression, prior use of neoadjuvant cisplatin-based chemotherapy, and nodal status.

The primary endpoint was disease-free survival in the intent-to-treat population and in the subset of patients with tumor PD-L1 expression of at least 1%. Approximately 40% of patients in each arm had tumor PD-L1 expression greater than or equal to 1%. Secondary endpoints included non–urothelial tract recurrence–free survival, and exploratory endpoints included distant metastasis–free survival.

In August 2021, nivolumab became the first adjuvant immunotherapy to receive U.S. Food and Drug Administration approval for the treatment of patients with urothelial carcinoma at high risk of recurrence after radical resection.

Disease-Free Survival Benefit Maintained

In the analysis with longer follow-up (minimum of 11 months) reported at the AUA 2022 Annual Meeting, the disease-free survival benefit with nivolumab was maintained with a similar effect size. In the intent-to-treat population and in patients with tumor PD-L1 expression greater than 1%, nivolumab was ­associated with an improvement in disease-free survival compared with placebo (hazard ratio [HR] = 0.7 and HR = 0.5, respectively).

The disease-free survival benefit with adjuvant nivolumab was seen across various subgroups, including those based on patient-related factors such as age, gender, and performance status, as well as across different tumor-related characteristics, such as pathologic staging and PD-L1 expression.

In addition, nivolumab was associated with an improvement in secondary endpoints, including non–urothelial track recurrence–free survival in the intent-to-treat population (HR = 0.71) and in patients with tumor PD-L1 expression greater than or equal to 1% (HR = 0.54.)

Finally, there was an improvement in the exploratory endpoint of distant metastasis–free survival, both in the intent-to-treat population and in the subset of patients with tumor PD-L1 expression greater than or equal to 1%. As expected, said Dr. Galsky, a higher proportion of patients in the placebo arm received subsequent postprotocol systemic therapy (23.9% of patients received immunotherapy on the placebo arm vs 7.9% of patients on the nivolumab arm).

DISCLOSURE: The CheckMate 274 trial was funded by Bristol Myers Squibb. Dr. Galsky reported financial relationships with BioMotiv, Janssen Pharmaceuticals, GlaxoSmithKline, Eli Lilly and Company, Astellas Pharma, Pfizer, EMD Serono, Seagen, Incyte Corporation, Aileron Therapeutics, Dracen Pharmaceutical, Inovio Pharmaceuticals, Numab AG, Dragonfly Therapeutics, Basilea Pharmaceutica AG, UroGen Pharma, Infinity Pharmaceuticals, Gilead Sciences, Rappta Therapeutics, Janssen Oncology, Dendreon, Novartis, Bristol Myers Squibb, Merck, AstraZeneca, and Genentech/Roche.

REFERENCE

1. Galsky M, Witjes JA, Gschwend JE, et al: Disease-free survival with longer follow-up from the CheckMate 274 trial of adjuvant nivolumab in patients after surgery for high-risk muscle-invasive urothelial carcinoma. 2022 American Urological Association Annual Meeting. Abstract PD10-01. Presented May 13, 2022.