Immunotherapy in Cervical Cancer

Current FDA-Approved Immunotherapy Options

The American Society of Clinical Oncology recommends pembrolizumab in combination with platinum-based chemotherapy with or without bevacizumab as the standard of care for patients with persistent, recurrent, or metastatic PD-L1-positive (CPS≥1) cervical cancer 1, 2
Pembrolizumab has two approved indications for cervical cancer: as monotherapy for recurrent or metastatic cervical cancer with PD-L1 CPS≥1 that has progressed on or after chemotherapy, and in combination with platinum-based chemotherapy with or without bevacizumab for persistent, recurrent, or metastatic PD-L1-positive (CPS≥1) cervical cancer 1, 2, 3
The KEYNOTE-826 trial demonstrated improved progression-free survival (PFS): 10.4 months vs 8.2 months (HR 0.62) 1
The KEYNOTE-826 trial also demonstrated improved overall survival (OS) across all populations studied 3
The KEYNOTE-826 trial showed a higher objective response rate (ORR): 68.1% vs 50.2% in PD-L1 CPS≥1 group 4
The KEYNOTE-826 trial demonstrated a longer duration of response: 18.0 months vs 10.4 months 4

The National Comprehensive Cancer Network strongly recommends PD-L1 testing for all patients with advanced/recurrent cervical cancer 1, 2
PD-L1 CPS≥1 is the established biomarker for pembrolizumab eligibility 3
Additional biomarker testing to consider includes MMR IHC (mismatch repair immunohistochemistry) and NGS for MSI (microsatellite instability) and TMB (tumor mutational burden) 1, 2, 5
TMB-H (≥10 mut/Mb) and MSI-H/dMMR tumors may be eligible for tissue-agnostic pembrolizumab treatment 3

For patients with persistent, recurrent, or metastatic cervical cancer and PD-L1 CPS ≥1, treatment-naïve patients should receive pembrolizumab + platinum-based chemotherapy ± bevacizumab 1, 2
For patients with persistent, recurrent, or metastatic cervical cancer and PD-L1 CPS ≥1, patients who have progressed on chemotherapy should receive pembrolizumab monotherapy 5, 6
For patients with persistent, recurrent, or metastatic cervical cancer and PD-L1 CPS <1, the standard of care is chemotherapy ± bevacizumab 5, 6

Treatment-related adverse events with pembrolizumab combination therapy include grade 3-5 adverse events: 81.8% (pembrolizumab group) vs 75.1% (placebo group) 1, 2
The most common serious adverse events with pembrolizumab combination therapy are anemia, neutropenia, decreased neutrophil count, and hypertension 3
Immune-related adverse events occur in 33.9% (11.4% grade 3-5) of patients in the pembrolizumab group vs 15.2% (2.9% grade 3-5) in the placebo group 1

ICI combinations showing promise in early-phase trials include balstilimab (anti-PD-1) + zalifrelimab (anti-CTLA-4) with an ORR of 25.6% in a phase II trial 7
Ipilimumab (anti-CTLA-4) + nivolumab (anti-PD-1) has shown positive results regardless of PD-L1 expression 7
Bintrafusp alfa (bifunctional fusion protein targeting PD-L1 and TGF-β) has an ORR of 28.2% and a duration of response of 11.7 months 7

The prevalence of MSI-H in cervical cancer is 2-12% 2
The prevalence of PD-L1 CPS≥1 in cervical cancer is high 3
Clinical trial enrollment should be encouraged for all patients with cervical cancer, especially those with limited standard treatment options 4, 5