In interim analyses of a Chinese phase III trial (COMPASSION-16) reported in The Lancet, Wu et al found that the addition of cadonilimab, a bispecific antibody targeting PD-1 and CTLA-4, to platinum-based chemotherapy with or without bevacizumab significantly improved progression-free and overall survival in the first-line treatment of patients with persistent, recurrent, or metastatic cervical cancer.
Study Details
In the multicenter double-blind trial, 445 women were randomly assigned between September 2021 and June 2022 to receive cadonilimab at 10 mg/kg (n = 222) or placebo (n = 223) plus platinum-based chemotherapy (cisplatin at 50 mg/m2 or carboplatin at AUC 4–5) plus paclitaxel at 175 mg/m2 with or without bevacizumab (15 mg/kg) every 3 weeks for six cycles. This regimen was followed by cadonilimab or placebo with or without bevacizumab every 3 weeks as maintenance therapy for up to 2 years. Use of cisplatin (41% vs 45%) or carboplatin (59% vs 55%) and bevacizumab (60% vs 59%) or no bevacizumab was decided by investigators prior to randomization. The primary endpoints were progression-free survival on blinded independent central review and overall survival.
Key Findings
Median follow-up for interim analysis of progression-free survival was 17.9 months (interquartile range [IQR] = 15.9–20.2 months). Median progression-free survival was 12.7 months (95% confidence interval [CI] = 11.6–16.1 months) in the cadonilimab group vs 8.1 months (95% CI = 7.7–9.6 months) in the control group (hazard ratio [HR] = 0.62, 95% CI = 0.49–0.80, P < .0001).
Median follow-up for the interim analysis of overall survival was 25.6 months (IQR = 23.6–28.0 months). Median overall survival was not reached (95% CI = 27.0 months to not estimable) in the cadonilimab group vs 22.8 months (95% CI = 17.6–29.0 months) in the control group (HR = 0.64, 95% CI = 0.48–0.86, P = .0011). The rate at 24 months was 62.2% vs 48.4%.
Grade ≥ 3 treatment-related adverse events occurred in 82% of the cadonilimab group and in 79% of the control group. The most common treatment-related adverse events in both groups were decreased neutrophils (41% vs 46%), decreased white blood cells (28% vs 36%), and anemia (17% vs 26%). Grade ≥ 3 immune-related adverse events occurred in 10% vs less than 1% of patients (no grade 5 events). Treatment-related death occurred in 4% of patients in the cadonilimab group and 3% of the control group.
The investigators concluded: “The addition of cadonilimab to first-line standard chemotherapy significantly improved progression-free survival and overall survival with a manageable safety profile in participants with persistent, recurrent, or metastatic cervical cancer. The data support the use of cadonilimab plus chemotherapy as an efficacious first-line therapy in persistent, recurrent, or metastatic cervical cancer.”
Xiaohua Wu, MD, PhD, of the Department of Gynecologic Oncology, Fudan University Shanghai Cancer Center, Shanghai, is the corresponding author of The Lancet article.
Disclosure: The study was funded by Akeso Biopharma. For full disclosures of all study authors, visit TheLancet.com.
