Subsequent systemic therapy with the immune checkpoint inhibitor nivolumab may offer overall survival benefit in patients with muscle-invasive urothelial carcinoma who underwent surgery to remove their tumors, according to recent findings presented by Geynisman et al at the 2024 ASCO Genitourinary Cancers Symposium (Abstract 528).
Background
Although the majority of urothelial carcinoma cases are not muscle-invasive, about one-quarter of the tumors are muscle-invasive at diagnosis. Currently, radical cystectomy or nephroureterectomy is the standard of care for patients with muscle-invasive urothelial carcinoma.
“The goal of adjuvant therapy is to prolong a patient’s disease-free survival and, ideally, improve their overall survival,” explained lead study author Daniel M. Geynisman, MD, Chief of the Division of Genitourinary Medical Oncology at Fox Chase Cancer Center.
In the CheckMate 274 trial, researchers randomly assigned patients with muscle-invasive urothelial carcinoma to receive adjuvant nivolumab or placebo. They showed that nivolumab significantly prolonged disease-free survival; however, data on whether or not nivolumab may prolong overall survival are unavailable.
Study Methods and Results
In a new analysis, investigators sought to determine how many patients with high-risk muscle-invasive urothelial carcinoma who underwent radical cystectomy could be cured with adjuvant nivolumab. The investigators defined a cure as 5-year survival without disease recurrence.
“Disease recurrence after 5 years in urothelial carcinoma is rare; almost all recurrences occur within the first 5 years,” Dr. Geynisman stressed. “In the absence of randomized clinical trial data that show if there is an overall survival benefit for adjuvant therapy, we tried to estimate the benefit of adjuvant nivolumab as it relates to [a] long-term cure,” he continued.
Dr. Geynisman and his colleagues used a mixture cure mathematical model to measure survival curves in patients assigned to receive either nivolumab or placebo who were considered cured or not cured. The investigators noted that disease-free survival among the cured subgroup in each arm was estimated using background mortality rates published by the World Health Organization and that disease-free survival among the uncured subgroup in each arm was obtained via mixture cure models along with the cure fractions using the reported disease-free survival data for each arm from the CheckMate 274 trial.
The investigators discovered that among all patients involved in the analysis, the model estimated a 6% to 9% absolute increase in the cure rates when patients were treated with adjuvant nivolumab compared with placebo. Between 43% and 45% of the patients who received nivolumab were cured compared with 36% to 37% of those who received placebo.
Additionally, among the patients with higher PD-L1 expression, there was a 23% to 25% absolute increase in the cure rate with nivolumab compared with placebo. Between 59% and 61% of the patients treated with nivolumab were cured compared with 36% to 37% of those who received placebo.
Conclusions
“Practically speaking, when physicians are talking to patients about whether or not to treat their urothelial carcinoma with adjuvant nivolumab, this is another piece of evidence to support doing so,” Dr. Geynisman underscored. “Although we don’t have mature overall survival data from the [CheckMate 274] trial, this model seems to support an overall survival benefit associated with adjuvant nivolumab,” he concluded.
Disclosure: For full disclosures of the study authors, visit meetings.asco.org.
