Phase 3 trial studies cadonilimab combination in recurrent or metastatic cervical cancer

Evidence before this study

The standard-of-care therapy for metastatic, persistent, or recurrent cervical cancer is platinum-based chemotherapy with or without bevacizumab, established by the phase 3 trials JCOG0505 and GOG 240, and pembrolizumab plus standard of care for those with PD-L1-positive expression, established by KEYNOTE-826. We searched PubMed for clinical trial articles, using the terms “recurrent or metastatic cervical cancer OR metastatic cervical cancer OR recurrent cervical cancer OR advanced cervical cancer”, and “phase 3” in the title or abstract, with a time limit from Jan 1, 2010, to Aug 9, 2024. Our search identified 43 abstracts, and—besides JCOG0505, GOG 240, and KEYNOTE-826—two additional randomised phase 3 trials of first-line treatment in metastatic, persistent, or recurrent cervical cancer were identified: BEATcc and AGO-Zervix-1. BEATcc found that adding atezolizumab to chemotherapy and bevacizumab significantly improved survival in metastatic, persistent, or recurrent cervical cancer, but the trial was limited by excluding participants with contraindication to bevacizumab, and around 40% of participants were ineligible to receive bevacizumab. AGO-Zervix-1 compared the use of topotecan and paclitaxel with topotecan and cisplatin, and found that platinum-based chemotherapy remains the standard-of-care chemotherapy regimen for individuals with recurrent or metastatic cervical cancer.

Added value of this study

In this COMPASSION-16 phase 3 trial, adding cadonilimab to platinum-based chemotherapy with or without bevacizumab significantly improved progression-free survival and overall survival in participants with metastatic, persistent, or recurrent cervical cancer. To our knowledge, this is the first phase 3 trial to show the efficacy of a PD-1 and CTLA-4 bispecific antibody in cervical cancer. In this study, we enrolled participants with metastatic, persistent, or recurrent cervical cancer regardless of PD-L1 expressing status and the treatment regimen included combined with or without bevacizumab, expanding the population of participants compared with those assessed in the KEYNOTE-826 and BEATcc studies. The findings suggest that adding cadonilimab to platinum-based chemotherapy with or without bevacizumab could bring survival benefit for individuals who are PD-L1 positive and negative, and for those who could (not) receive bevacizumab treatment. Previous clinical trials included mostly White participants or were conducted in high-income regions, and the current study added more evidence in an Asian population and in a middle-income country.

Implications of all the available evidence

The COMPASSION-16 trial addressed an unmet need in individuals with metastatic, persistent, or recurrent cervical cancer. Cadonilimab plus chemotherapy with or without bevacizumab could be an effective and safe first-line treatment option for individuals with metastatic, persistent, or recurrent cervical cancer.

Source: The Lancet