Efficacy and Safety of Immunotherapy for Cervical Cancer-A Systematic Review of Clinical Trials

Simple Summary Cervical cancer is the 4th leading cause of cancer deaths in women worldwide. Surgery, chemotherapy, radiotherapy and chemoradiation therapy are routinely used in the treatment of cervical cancer, while immunotherapy remains a novelty. The aim of our systematic review was to provide an extensive overview of the efficacy and safety of immunotherapy in cervical cancer patients. A total of 50 clinical trials assessed immune checkpoint inhibitors, therapeutic vaccines and adaptive cell transfer therapy. Overall, immunotherapy showed an acceptable safety profile. While the level of evidence on efficacy is still low, promising results, including few complete remissions in heavily pretreated women with metastatic disease, have been observed. Furthermore, a recent phase III trial assessing pembrolizumab in combination with chemotherapy (+/- bevacizumab) demonstrated a prolonged overall survival and has now led to a new standard of care for first-line systemic treatment in persistent, metastatic or recurrent cervical cancer patients. Purpose: To systematically review the current body of evidence on the efficacy and safety of immunotherapy for cervical cancer (CC). Material and Methods: Medline, the Cochrane Central Register of Controlled Trials and Web of Science were searched for prospective trials assessing immunotherapy in CC patients in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Full-text articles in English and German reporting outcomes of survival, response rates or safety were eligible. Results: Of 4655 screened studies, 51 were included (immune checkpoint inhibitors (ICI) n=20; therapeutic vaccines n = 25; adoptive cell transfer therapy n=9). Of these, one qualified as a phase III randomized controlled trial and demonstrated increased overall survival following treatment with pembrolizumab, chemotherapy and bevacizumab. A minority of studies included a control group (n = 7) or more than 50 patients (n = 15). Overall, response rates were low to moderate. No response to ICIs was seen in PD-L1 negative patients. However, few remarkable results were achieved in heavily pretreated patients. There were no safety concerns in any of the included studies. Conclusion: Strong evidence on the efficacy of strategies to treat recurrent or metastatic cervical cancer is currently limited to pembrolizumab in combination with chemotherapy and bevacizumab, which substantiates an urgent need for large confirmatory trials on alternative immunotherapies. Overall, there is sound evidence on the safety of immunotherapy in CC.