Nivolumab (Opdivo) improved disease-free survival (DFS), non-urothelial tract recurrence-free survival (NUTRFS), and disease-specific survival compared with placebo in patients with high-risk muscle-invasive urothelial carcinoma Extended follow-up results from the phase 3 CheckMate 274 trial (NCT02632409) presented in continued to demonstrate benefit of duration (DSS) after definitive surgery 2023 Urogenital Cancer Symposium.
According to the lead author of the Phase 3 CheckMate 274 trial, “These results further support adjuvant nivolumab as the standard of care for patients with muscle-invasive urothelial carcinoma who are at high risk of recurrence after definitive surgery.”
In the ITT population with median follow-up of 36.1 months and 33.9 months, respectively, nivolumab continued to improve DFS versus placebo, including in patients with PD-L1 expression ≥1%.Median DFS in the nivolumab group was 22.0 months (95% CI, 18.8-36.9) vs. 10.9 months in the placebo group (95% CI, 8.3-15.2) (hazard ratio [HR], 0.71; 95% CI, 0.58–0.86). In the population with PD-L1 expression ≥1%, median DFS was 52.6 months (95% CI, 25.8 – not estimable). [NE]) and 8.4 months (95% CI, 5.6-17.9), respectively (HR, 0.52; 95% CI, 0.37-0.72).
The 24-month and 36-month DFS rates for nivolumab and placebo were 48.4% vs. 38.8% and 45.0% vs. 34.9%, respectively, in the ITT population. In the PD-L1 population, the proportions were 60.3% vs. 37.6% and 56.9% vs. 33.3%, respectively.
“These results further support adjuvant nivolumab as the standard of care for patients with muscle-invasive urothelial carcinoma at high risk of recurrence after definitive surgery,” said lead author, professor of medicine and director of the Department of Genitourinary Oncology. said Matthew Galsky, MD of , and he is co-director of the Bladder Cancer Center of Excellence at the Tisch Cancer Institute, Mount He is also the Translational Vice Director of Research at the Tisch Cancer Institute in Sinai.
Nivolumab was administered in all prespecified patient subgroups, including those based on age, sex, region, performance status, minor histologic differences, pathologic nodal status, and pathologic T stage. It was preferred over placebo, Galsky noted.
A randomized, double-blind, multicenter trial included patients with ypT2 to ypT4a or ypN-positive disease previously treated with neoadjuvant cisplatin. Eligible patients had undergone radical surgery within the previous 120 days and he achieved disease-free status within 4 weeks from randomization.
Patients were randomized 1:1 to receive intravenous nivolumab 240 mg every 2 weeks or placebo followed by adjuvant therapy for up to 1 year. Stratification factors included her PD-L1 status of tumor, her previous neoadjuvant cisplatin-based chemotherapy, and lymph node status.
Primary endpoints were DFS in ITT and PD-L1 in ≥1% of the population; secondary endpoints included NUTRFS, DSS and overall survival. Exploratory endpoints included distant metastasis-free survival (DMFS), progression-free survival (PFS2), safety, and health-related quality of life.
The median age in the nivolumab and placebo groups was 65.3 years versus 65.9 years, respectively. Most patients were Caucasian (75% vs. 76%), had an ECOG performance status of 0 (63% vs. 62%), and had tumors of bladder origin (79% vs. 79%).
In the ITT population, median NUTRFS was 25.9 months (95% CI, 19.4-44.0) with nivolumab and 13.7 months (95% CI, 8.4-20.3) with placebo (HR, 0.72; 95% CI, 0.59- 0.88). In patients with PD-L1 expression ≥1%, median NUTRFS was 52.6 months (95% CI, 29.7-NE) vs. 8.4 months (95% CI, 5.6-20.0), respectively (HR, 0.53; 95% CI, 0.38–0.74).
Additionally, the 24-month and 36-month NUTRFS rates in the nivolumab and placebo groups were 51.6% vs. 42.2% and 47.5% vs. 38.3%, respectively. The proportions of groups with PD-L1 expression ≥1% were 62.7% vs 38.3% and 57.4% vs 34.8%, respectively.
Median DMFS in the nivolumab group was 47.1 months (95% CI 26.5-NE) compared to 28.7 months (95% CI 16.6-47.8) in the placebo group (HR 0.74; 95% CI 0.60- 0.92). Additionally, the 24-month and 36-month DMFS rates were 57.8% vs. 51.2% and 53.9% vs. 47.0%, respectively.
Furthermore, in the nivolumab group, median DMFS was not reached in patients with PD-L1 ≥1% (NR; 95% CI, 44.0-NE) compared to 20.7 months (95% CI, 10.6- NE). placebo group (HR, 0.58; 95% CI, 0.40-0.84). The 24-month and 36-month DMFS rates were 66.4% vs. 48.6% and 61.7% vs. 44.2%, respectively.
Median PFS2 was 61.2 months (95% CI, 44.0-NE) with nivolumab vs. 47.1 months (95% CI, 29.4-65.2) with placebo in the ITT population (HR , 0.79; 95% CI, 0.63–0.98). Furthermore, in the PD-L1 subgroup after treatment with nivolumab, median PFS2 was NR (95% CI, NE-NE) compared to 39.4 months (95% CI, 25.2-NE; HR, 0.54; 95% CI, 0.37-0.79). placebo respectively.
The 24-month and 36-month PFS2 rates with nivolumab and placebo were 71.4% vs. 60.7% and 61.0% vs. 53.8% in the ITT population and 78.8% vs. 59.3% and 70.6% vs. 51.4% in the PD-L1 population, respectively . subgroup.
Galsky summarized how efficacy results changed over time.
“[When examining] Examining efficacy results over time from initial report with a minimum follow-up of 5.9 months to current presentation with a minimum follow-up of 31.6 months, across primary, secondary, and exploratory endpoints And the adjuvant nivolumab versus placebo effect is very stable over time,” he said. “It’s important to point out that this is a fixed duration treatment, limited to one year of adjuvant treatment with sustained effects over time.”
A total of 79% of patients experienced any grade of treatment-related adverse reaction (TRAE) in the nivolumab group compared to 56% in the placebo group, with 18% and 7% experiencing grade 3 or higher toxicity, respectively. Additionally, 14% of patients and 2% of patients, respectively, experienced any grade of his TRAE leading to discontinuation.
Common TRAEs in the nivolumab group included pruritus (23%), fatigue (17%), and diarrhea (17%), along with increased lipase (5%) and increased amylase (4%). There were grade 3 or higher toxicities, including Common TRAEs of any grade in the placebo group were fatigue (12%), pruritus (11%) and diarrhea (11%). Grade 3 or higher toxicities in the control group included increased lipase (3%) and increased amylase (1%).
reference
Galsky M, Witjes JA, Gschwend J, et al. Long-term follow-up results from the CheckMate 274 trial. J Clin On Call2023;41(suppl 6):LBA443.doi:10.1200/JCO.2023.41.6_suppl.LBA443