The phase 3 COMPASSION-16 trial, published in The Lancet, reveals that adding cadonilimab (AK104) to platinum-based chemotherapy, with or without bevacizumab, significantly improves survival outcomes in patients with persistent, recurrent, or metastatic cervical cancer. The study marks a significant advancement in the first-line treatment of this challenging disease.
The randomized, double-blind, placebo-controlled trial enrolled 445 women across 59 clinical sites in China. Patients received either cadonilimab at 10 mg/kg or placebo in combination with platinum-based chemotherapy (cisplatin at 50 mg/m2 or carboplatin at an area under the curve of 4-5 plus paclitaxel at 175 mg/m2) with or without bevacizumab at 15 mg/kg every 3 weeks for 6 cycles, followed by maintenance therapy with cadonilimab or placebo with or without bevacizumab every 3 weeks.
Progression-Free Survival
At a data cutoff date of September 4, 2023, and a median follow-up of 17.9 months, the median progression-free survival (PFS) per blinded independent central review (BICR) was 12.7 months (95% CI, 11.6-16.1) among patients who received cadonilimab (n = 222) vs 8.1 months (95% CI, 7.7-9.6) among those who received placebo (n = 223; HR, 0.62; 95% CI, 0.49-0.80; P < .0001). Investigator-assessed PFS outcomes were consistent with the BICR-assessed results.
Overall Survival
At a data cutoff of April 30, 2024, and a median follow-up of 25.6 months, the median overall survival (OS) was not reached (NR; 95% CI, 27.0 months-not evaluable) vs 22.8 months (95% CI, 17.6-29.0) in the cadonilimab and placebo arms, respectively (HR, 0.64; 95% CI, 0.48-0.86; P = .0011). The 24-month OS rates were 62.2% (95% CI, 55.2%-68.5%) in the cadonilimab arm and 48.4% (95% CI, 41.1%-55.4%) in the placebo arm.
Expert Commentary
"COMPASSION-16 (AKT104-303) is the first phase 3 study to show that adding cadonilimab to chemotherapy with or without bevacizumab significantly and clinically meaningfully improved PFS and OS in first-line advanced cervical cancer," wrote lead study author Xiaohua Wu, MD, a professor and chair of the Department of Gynecologic Oncology at Fudan University Shanghai Cancer Center in China.
Additional Findings
The BICR-assessed PFS outcomes favored the cadonilimab arm vs the placebo arm across all prespecified subgroups. Among patients with a PD-L1 CPS of at least 1, the median PFS was 13.5 months (95% CI, 10.8-17.3) vs 8.3 months (95% CI, 7.5-9.7 [HR, 0.62; 95% CI, 0.46-0.83]).
Notably, among patients who did not receive bevacizumab, the median PFS was 11.7 months in the cadonilimab arm vs 6.9 months in the placebo arm (HR, 0.46; 95% CI, 0.32-0.66). "We speculate that the efficacy shown in the subgroup without bevacizumab use could be attributable to the combined anti–PD-1 and anti–CTLA-4 activity of cadonilimab," the authors noted. "Cadonilimab might offer a suitable treatment option for individuals who are not eligible for bevacizumab therapy."
Safety Profile
Treatment-emergent adverse effects (TEAEs) were observed in over 99% of treated patients in the cadonilimab arm and 100% of those in the placebo arm. Grade 3 or higher TEAEs occurred in 85% and 80% of patients in these respective arms. The most common AEs in the cadonilimab arm were anemia, decreased white blood cell counts, and decreased neutrophil counts.
Limitations
The authors noted that one limitation of this trial was the homogeneity of the patient demographics, since the trial was conducted in China and only included patients who were ethnically Chinese.
Conclusion
"COMPASSION-16 is the largest first-line cervical cancer trial conducted in an Asian population to date, and the findings provided valuable evidence in the treatment of advanced cervical cancer in this population," the authors concluded.
