Vascular endothelial growth factor (VEGF) has emerged as a therapeutic target in 
several malignancies, including cervical cancer. Chemotherapy doublets combined 
with the fully humanized monoclonal antibody, bevacizumab, now constitute 
first-line therapy for women struggling with recurrent/metastatic cervical 
carcinoma. Regulatory approval for this indication was based on the phase III 
randomized trial, GOG 240, which demonstrated a statistically significant and 
clinically meaningful improvement in overall survival when bevacizumab was added 
to chemotherapy: 17.0 vs 13.3 months; HR 0.71; 98% CI, 0.54-0.95; p = .004. 
Incorporation of bevacizumab resulted in significant improvements in 
progression-free survival and response. These benefits were not accompanied by 
deterioration in quality of life. GOG 240 identified vaginal fistula as a new 
adverse event associated with bevacizumab use. All fistulas occurred in women 
who had received prior pelvic radiotherapy, and none resulted in emergency 
surgery, sepsis, or death. Final protocol-specified analysis demonstrated 
continued separation of the survival curves favoring VEGF inhibition: 16.8 vs 
13.3 months; HR 0.77; 95% CI, 0.62-9.95; p = .007. Post-progression survival was 
not significantly different between the arms in GOG 240. Moving forward, 
immunotherapy has now entered the clinical trial arena to address the high unmet 
clinical need for effective and tolerable second line therapies in this patient 
population. Targeting the programmed cell death 1/programmed death ligand 1 
(PD-1/PD-L1) pathway using checkpoint inhibitors to break immunologic tolerance 
is promising. The immunologic landscape involving human papillomavirus-positive 
head and neck carcinoma and cutaneous squamous cell carcinoma can be informative 
when considering feasibility of checkpoint blockade in advanced cervical cancer. 
Phase II studies using anti-PD-1 molecules, nivolumab and pembrolizumab are 
ongoing, and GOG 3016, the first phase III randomized trial of a checkpoint 
inhibitor (cemiplimab) in cervical cancer, recently activated. Important 
considerations in attempts to inhibit the inhibitors include pseudoprogression 
and post-progression survival, abscopal effects, and immune-related adverse 
events, including endocrinopathies.