The anti-PD-1 era of cervical cancer: achievement, opportunity, and challenge

Area of Science:

• Oncology
• Immunotherapy
• Gynecologic Oncology

Background:

• Cervical cancer remains a significant global health challenge, particularly advanced stages with recurrence and metastasis.
• While surgery cures early-stage disease, advanced cases require novel treatment strategies.
• Anti-programmed death-1 (PD-1) therapies have transformed cancer treatment but show modest response rates as monotherapy for recurrent/metastatic cervical cancer (R/M CC).

Purpose of the Study:

• To review current clinical trials and studies on anti-PD-1 monotherapy and combination therapy for cervical cancer.
• To discuss the molecular mechanisms underlying combination immunotherapies.
• To provide evidence supporting anti-PD-1 use and insights into novel combination strategies for cervical cancer treatment.

Main Methods:

• Review of published studies and ongoing clinical trials involving anti-PD-1 agents in cervical cancer.
• Analysis of combination therapies including chemotherapy, targeted therapy, and other immunotherapies.
• Evaluation of dual PD-1/CTLA-4 antibodies and the role of anti-PD-1 in sensitizing radiotherapy.

Main Results:

• Pembrolizumab, an anti-PD-1, is approved for second-line R/M CC with a ~15% response rate.
• Combination therapies involving anti-PD-1 agents are under active clinical investigation.
• Dual PD-1/CTLA-4 antibodies demonstrate superior efficacy compared to anti-PD-1 monotherapy in cervical cancer trials.
• Anti-PD-1 can enhance the efficacy of radiotherapy.

Conclusions:

• Anti-PD-1 therapies, especially in combination, represent a promising advancement for treating advanced cervical cancer.
• Further research into combination strategies and their molecular mechanisms is crucial for optimizing treatment outcomes.
• Understanding anti-PD-1's role is key to guiding clinical applications and developing more effective immunotherapies for cervical cancer.