Adding cadonilimab to platinum-based chemotherapy significantly improves both progression-free survival (PFS) and overall survival (OS) in patients with persistent, recurrent, or metastatic cervical cancer, according to the results of the phase 3 COMPASSION-16 trial published in The Lancet. The study suggests a potential new treatment option for this patient population, particularly those with PD-L1 positive tumors.
The COMPASSION-16 trial (NCT04982237) enrolled 445 women in China, aged 18-75, with persistent, recurrent, or metastatic cervical cancer. Participants were randomized to receive either cadonilimab at 10 mg/kg (n=222) or placebo (n=223), in combination with platinum-based chemotherapy (cisplatin or carboplatin plus paclitaxel), with or without bevacizumab, every 3 weeks for 6 cycles, followed by maintenance therapy every 3 weeks for up to 2 years.
Baseline characteristics were well-balanced between the treatment arms. The median age was 56 years, 83% had squamous cell carcinoma, 73% had metastatic disease, and 48% had received prior concurrent chemoradiotherapy.
Progression-Free Survival
At a median follow-up of 17.9 months for the interim PFS analysis, cadonilimab significantly improved PFS. Median PFS was 12.7 months in the cadonilimab arm versus 8.1 months in the placebo arm (HR, 0.62; 95% CI, 0.49-0.80; P <.0001). Subgroup analysis indicated that the PFS improvement was not observed in patients with a PD-L1 combined positive score below 1, those who received bevacizumab, or those who had not received prior concurrent chemoradiotherapy.
Overall Survival
With a median follow-up of 25.6 months, the final analysis showed a significant improvement in OS with cadonilimab. Median OS was not reached in the cadonilimab arm and was 22.8 months in the placebo arm (HR, 0.64; 95% CI, 0.48-0.86; P =.0011). The 24-month OS rates were 62.2% and 48.4%, respectively. OS favored the cadonilimab arm across subgroups.
Safety Profile
Treatment-related adverse events (TRAEs) occurred in nearly all patients in both arms. Grade 3 or higher TRAEs were reported in 82% of patients in the cadonilimab arm and 79% in the placebo arm. The most common grade 3 or higher TRAEs in the cadonilimab and placebo arms, respectively, were decreased neutrophil count (40.7% and 46.1%), decreased white blood cell count (28.3% and 36.1%), and anemia (15.9% and 24.2%). There were 9 fatal TRAEs in the cadonilimab arm and 6 in the placebo arm.
Implications
The study's authors concluded that cadonilimab plus chemotherapy, with or without bevacizumab, represents a potentially effective and safe treatment option for patients with persistent, recurrent, or metastatic cervical cancer. Cadonilimab is currently approved in China and has received orphan drug and fast track designations from the US FDA.
