Adjuvant Nivolumab as Standard of Care in Resected Bladder Cancer

SAN FRANCISCO — New findings lend further support to adjuvant nivolumab (Opdivo) as a standard of care for patients with metastatic urothelial cancer.

Extended follow-up data from the phase 3 CheckMate 274 trial continue to show that, compared with placebo, nivolumab improves disease-free survival, non-urothelial tract recurrence-free survival (NUTRFS), and distant metastasis-free survival (DMFS) in patients with high-risk, muscle-invasive urothelial cancer after undergoing radical surgery.

The benefit was observed in both in the intent-to-treat population (ITT) and in the subset of patients with programmed cell death–ligand1 (PD-L1) expression of at least 1%.

“In the ITT population, median disease-free survival with nivolumab was doubled compared to placebo,” said lead author Matthew Galsky, MD, director of genitourinary medical oncology and co-director of the Center of Excellence for Bladder Cancer at Tisch Cancer Institute, New York City. “For the patients with high PD-L1 expression, the median disease-free survival with nivolumab reached 52.6 months, more than 6 times that of the placebo arm.”

“These results further support adjuvant nivolumab as a standard of care in high-risk muscle-invasive urothelial cancer after resection,” he concluded.

Galsky presented the findings here at the 2023 American Society of Clinical Oncology Genitourinary Cancers Symposium.

Practice Changing

The earlier results of this study have already led to an approval from the US Food and Drug Administration. In August 2021, nivolumab became the first adjuvant immunotherapy for use in patients with urothelial carcinoma at high risk for recurrence after radical resection

“This is a practice-changing study,” said Scot Niglio, MD, medical oncologist, NYU Perlmutter Cancer Center, New York City, who was approached for an independent comment.

“For decades, there were limited to zero treatment options in the postsurgical setting for urothelial cancer patients with a high recurrence risk,” he said.

The standard of care for muscle-invasive urothelial carcinoma is surgery, which may include neoadjuvant cisplatin-based chemotherapy, but most patients will experience disease recurrence, he explained

“When urothelial cancer recurs outside the urinary tract, the prognosis quickly changes from curable to incurable,” he said, “making this area of research paramount.”

Niglio emphasized that these updated results show continued benefit from nivolumab on disease-free survival, as well as non-urothelial tract recurrence-free survival and distant metastasis-free survival, supporting its use as standard-of-care therapy.

“Even though the overall survival data is still maturing, the current data remains promising,” he said. “Patients with urothelial cancer meeting the criteria for high risk now have a treatment option to mitigate the potential of distant recurrence.”

In his own practice, Niglio added that he will “continue to discuss adjuvant nivolumab as a potential treatment option with all patients who are eligible based on this study.”

Met All Endpoints

The Checkmate 274 trial involved 353 patients (of whom 140 patients had PD-L1 ≥ 1%) randomly assigned to take nivolumab 240 mg every 2 weeks and 356 patients (with 142 patients with PD-L1 ≥ 1%) randomized to placebo. All patients had pathologic evidence of urothelial cancer at high risk of recurrence and Eastern Cooperative Oncology Group performance status (ECOG PS) ≤ 1.

Previous results, at a median follow-up of about 20 months, show that the study met its primary endpoint, showing significant prolongation of disease-free survival in the intention-to-treat population, with nivolumab at 21 months vs placebo at 10.9 months (hazard ratio [HR], 0.70; P < .001), as reported by Medscape Medical News.

When the analysis considered only patients with tumors expressing PD-L1 ≥ 1%, the median disease-free survival was even higher, not reached vs 10.8 months (HR, 0.53; P < .001).

Nivolumab was also superior to placebo for NUTRFS, in both in the entire ITT population and in the subset with PD-L1–positive tumors.

The latest results come from a median follow-up of 36.1 months. The median disease-free survival was 22 months with nivolumab compared with 10.9 months with placebo in ITT patients, and 52.6 months on nivolumab vs 8.4 months in patients with PD-L1 ≥ 1%.

Nivolumab was superior to placebo for secondary and exploratory endpoints, NUTRFS (ITT: HR, 0.72; PD-L1 ≥ 2%: HR, 0.53) and DMFS (ITT: HR, 0.74; PD-L1 ≥ 2%: HR, 0.58). However, overall survival data remained immature and will be assessed as a future data cutoff, Galsky explained.

The updated analysis also included another exploratory endpoint, progression-free survival 2 (PFS2), defined as:

time from randomization to disease progression after subsequent next-line systemic therapy;
start of second subsequent next-line systemic therapy; or
death

Median PFS2 was 61.2 months for all-patients who received nivolumab vs 47.1 months with placebo (HR, 0.79). In the PD-L1 ≥ 1% subgroup, median PFS2 was not reached with nivolumab vs. 39.4 months with placebo (HR, 0.54).

Grade 3-4 treatment-related adverse events occurred in 18.2% and 7.2% of patients (nivolumab vs placebo), and this was consistent with the primary analysis. “No new safety signals were identified,” said Galsky.

The CheckMate 274 trial was funded by Bristol-Myers Squibb, manufacturer of nivolumab. Galsky reported 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.

2023 Genitourinary Cancers Symposium: Abstract LBA443. Presented February 17, 2023.

Roxanne Nelson is a registered nurse and an award-winning medical writer who has written for many major news outlets and is a regular contributor to Medscape.

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