The American Society of Clinical Oncology (ASCO) recently held its 2023 Genitourinary Cancers Symposium in San Francisco, California. The meeting focused on multidisciplinary approaches in GU cancer treatment, research, and care. Previously, the latest data in first-line treatments for locally advanced or metastatic urothelial carcinoma were discussed. Herein are new data in adjuvant therapy for high-risk non-muscle-invasive bladder cancer (NMIBC) and localized muscle-invasive urothelial carcinoma (MIUC).

High-Risk Non-Muscle-Invasive Bladder Cancer 

Current standard of care for high-risk NMIBC is transurethral resection of the bladder tumor (TURBT), followed by therapy with intravesical bacillus Calmette-Guerin (BCG). Patients who do not respond to BCG or who relapse within 12 months of BCG therapy face a poor prognosis and require radical cystectomy. The multicohort phase 2 KEYNOTE-057 trial evaluated pembrolizumab monotherapy in patients with BCG-unresponsive high-risk NMIBC who were ineligible for radical cystectomy. Data from Cohort A (carcinoma in situ [CIS] with or without papillary tumors) from this trial led to the US FDA approval of pembrolizumab in this setting. At ASCO GU 2023, Andrea Necchi, MD (Vita-Salute San Raffaele University, IRCCS San Raffaele Hospital and Scientific Institute, Milan, Italy) presented the data from Cohort B.

Cohort B consisted of patients with papillary tumors only who had already undergone TURBT before receiving 200 mg of IV pembrolizumab every 3 weeks for up to 2 years. They remained on treatment until disease recurrence or progression. The primary endpoint was 12-month disease-free survival (DFS) and safety. The cohort included 132 patients at 54 sites. At the time of data cutoff, the median follow-up was 45.4 months (range, 14.9 – 77.1). Among the cohort, 83 patients (63%) experienced recurrence, progression, or death in a median of 7.7 months (95% CI: 5.5, 13.6). The 12-month DFS rate was 43.5% (95% CI: 34.9, 51.9). The 24-month and 36-month DFS rates were both 35% (95% CI: 26.4, 43.4).

The authors concluded that pembrolizumab has a manageable safety profile, with no treatment-related deaths and stable quality of life during treatment. Based on sample size and follow-up duration, these results are among the most robust for a novel systemic therapy for papillary high-risk NMIBC. Data suggest that patients with papillary high-risk NMIBC who did not respond to BCG may benefit from pembrolizumab monotherapy.

Muscle-Invasive Urothelial Carcinoma

Based on the CheckMate 274 trial, adjuvant nivolumab became a standard of care for patients with high-risk MIUC following radical surgery. This phase 3 trial met both of its primary endpoints, increasing DFS in the intention-to-treat population and among patients with a PD-L1 expression level of ≥ 1% when compared with placebo. At ASCO GU 2023, Matthew D. Galsky, MD (Icahn School of Medicine at Mount Sinai, New York, US) presented the extended follow-up results from the CheckMate 274 trial.

With extended follow-up (median: 36.1 months),the median DFS was doubled with nivolumab compared with placebo in the intention-to-treat population (22.0 vs. 10.9 months; HR, 0.71). The PD-L1 population experienced even greater benefits: median DFS was 52.6 months with nivolumab vs. 8.4 months in the placebo group (HR, 0.52). The data were similar for median non-urothelial tract recurrence-free survival (NUTRFS) in the ITT group: 25.9 months for nivolumab vs. 13.7 months for placebo (HR, 0.72). In the PD-L1 population, the median NUTRFS was 52.6 months for nivolumab vs. 8.4 months for placebo (HR, 0.53).

In addition to PD-L1 status, nivolumab’s DFS benefit was seen in subgroups defined by age, sex, ECOG performance status, nodal status, and prior cisplatin-based chemotherapy. No new safety signals were identified. Grade 3–4 treatment-related adverse events occurred in 18.2% and 7.2% of patients in the nivolumab and placebo arms, consistent with the primary analysis. Upon extended follow-up, CheckMate 274 results further support adjuvant nivolumab as a standard of care for high-risk MIUC following radical resection.

The discussant, Michiel Van Der Heijden, MD, PhD (Netherlands Cancer Institute, Amsterdam, Netherlands) noted a concern that the DFS curves for the ITT population were converging after the cessation of therapy at 1 year. However, with this extended follow up, he concluded that the curves remain separated and the hazard ratios are stable. The PD-L1-positive subgroup is very convincing despite the lack of overall survival data. In Europe, only the PD-L1-positive subgroup was registered for nivolumab in this setting.