BACKGROUND AND PURPOSE:

• Pembrolizumab (brand name Keytruda), is an anti-programmed death 1 (PD-1) monoclonal antibody
  • PD-1 on lymphocytes normally prevents immune system from attacking other normal cells in the body (immune checkpoint) by binding to PD ligands (PD-L1) and deactivating cell-mediated immune response
  • Cancer cells can make PD-L1 and block person’s immune system from destroying the malignant cells
• Colombo et al. (NEJM, 2021) assessed the relative benefit of adding pembrolizumab to chemotherapy for persistent, recurrent or metastatic cervical cancer

METHODS:

• Double-blind, phase 3 trial
• Participants
  • Persistent, recurrent, or metastatic cervical cancer
  • Adenocarcinoma, adenosquamous carcinoma, or squamous-cell carcinoma
  • Not been treated with systemic chemotherapy
  • Not amenable to curative treatment
• Interventions
  • Pembrolizumab (200 mg) every 3 weeks, for up to 35 cycles, plus platinum-based chemotherapy and, per investigator discretion, bevacizumab (anti-VEGF monoclonal antibody)
  • Placebo and platinum-base chemotherapy
• Study design
  • 1:1 randomization
  • Stratified by metastatic disease at diagnosis, planned bevacizumab and programmed death ligand-1 (PD-L1) combined positive score (reflects likelihood of response to pembrolizumab)
• Primary outcome
  • Progression-free survival
  • Overall survival

RESULTS:

• 548 patients with a PD-L1 combined score of ≥1 or more
  • Median progression-free survival was significantly higher in patients in the pembrolizumab group, compared to the placebo group
    • Pembrolizumab: 10.4 months
    • Placebo: 8.2 months
    • Hazard ratio (HR) for disease progression or death 0.62 (95% CI, 0.50 to 0.77); P<0.001
  • Overall survival at 24 months was higher in the pembrolizumab group
    • Pembrolizumab: 53.0%
    • Placebo: 41.7%
    • HR for death 0.64 (95% CI, 0.50 to 0.81); P<0.001
• 617 patients in the intention to treat population
  • Median progression-free survival was significantly higher in patients in the pembrolizumab group, compared to the placebo group
    • Pembrolizumab: 10.4 months
    • Placebo: 8.2 months
    • HR 0.65 (95% CI, 0.53 to 0.79); P<0.001
  • Overall survival at 24 months was higher in the pembrolizumab
    • Pembrolizumab: 50.4%
    • Placebo: 40.4%
    • Hazard ratio 0.67 (95% CI, 0.54 to 0.84); P<0.001
• 317 patients in the PD-L1 combined positive score of ≥10
  • Median progression-free survival was significantly higher in patients in the pembrolizumab group, compared to the placebo group
    • Pembrolizumab: 10.4 months
    • Placebo: 8.1 months
    • Hazard ratio 0.58 (95% CI, 0.44 to 0.77); P<0.001
  • Overall survival at 24 months was higher in the pembrolizumab group
    • Pembrolizumab: 54.4%
    • Placebo: 44.6%
    • Hazard ratio 0.61 (95% CI, 0.44 to 0.84); P=0.001
• Adverse events
  • Anemia
    • Pembrolizumab: 30.3%
    • Placebo: 26.9%
  • Neutropenia
    • Pembrolizumab: 12.4%
    • Placebo: 9.7%

CONCLUSION:

• When combined with chemotherapy, patients with persistent, recurrent, or metastatic cervical cancer in the pembrolizumab group experienced a median progression-free and overall survival that was significantly longer than those in the placebo group
• The authors conclude

We found that adding pembrolizumab reduced the hazard of disease progression, as assessed by investigator review, or death by 38% in patients with a PD-L1 combined positive score of 1 or more, by 35% in the intention-to-treat population, and by 42% in patients with a PD-L1 combined positive score of 10 or more; the hazard of death was reduced by 36%, 33%, and 39%, respectively 

Learn More – Primary Sources:

Pembrolizumab for Persistent, Recurrent, or Metastatic Cervical Cancer