Balstilimab and other immunotherapy for recurrent and metastatic cervical cancer.

Abstract

Recurrent and metastatic cervical cancer is generally treated by cisplatin, paclitaxel, and bevacizumab with limited benefit this constituting an unmet need. Immune checkpoint inhibitors, namely the inhibitors of programmed death 1 and programmed death ligand 1 have been proved to be efficacious in the treatment of patients with advanced cervical cancer. Recently, a PD-1 inhibitor, pembrolizumab was approvedfor such cancer. However, there is much scope of improvement of current outcome. Dual blockade of cytotoxic T lymphocyte-associated protein 4 and PD-1 is an attractive therapeutic approach. It is used in other cancers and is currently proposed for cancer cervix also. Search is on for single or combined regimen showing efficacy in multiple pathological conditions of cancer cervix irrespective presence of PD-L1 in malignant tissue. An effort to meet such unmet need has culminated in inventing new immune checkpoint inhibitors namely PD-1 inhibitor, AGEN2034 (Balstilimab) and CTLA-4 inhibitor, AGEN1884 (Zalifrelimab).They have shown meaningful and durable activity as single-agent therapy in previously treated patients with persistent R/M CC in a large phase II trial (NCT03104699) in PD-L1 + and PD-L1- tumour. Responses were found both in squamous cell carcinoma & adenocarcinoma cell types. Balstilimab plus zalifrelimab combination (NCT03495882) produced improved clinical benefit over monotherapy as evidenced by higher relative response rates and longer response duration, as well as a manageable safety profile. Interesting development of this combination and other immunotherapies in R/M CC are discussed in this ensuing review.