Research Timeline on Pembrolizumab in Ovarian Cancer
The research on pembrolizumab (PD-1 inhibitor) in ovarian cancer primarily took place between 2019 and 2024, with the most significant clinical trials occurring in 2019.
Key Research Timeline
2019: KEYNOTE-100 Study
The landmark phase II KEYNOTE-100 study (NCT02674061) represents the most significant research on pembrolizumab in ovarian cancer 1. This study:
- Examined two patient cohorts with recurrent ovarian cancer
- Cohort A: patients with 1-3 prior treatment lines
- Cohort B: patients with 4-6 prior treatment lines
- Found modest activity with objective response rates of 7.4% for cohort A and 9.9% for cohort B
- Demonstrated correlation between higher PD-L1 expression and higher response rates
2020-2023: Combination Therapy Research
Research expanded to investigate pembrolizumab in combination with other agents:
- By 2020, pembrolizumab was recognized in NCCN guidelines for microsatellite instability-high (MSI-H) or deficient mismatch repair (dMMR) tumors 2
- 2023: Studies examined pembrolizumab combined with bevacizumab and oral cyclophosphamide in heavily pre-treated platinum-resistant ovarian cancer 3
- Showed 13% overall response rate and 33% disease control rate
- Demonstrated 3.5 months median progression-free survival
2024: Recent Developments
More recent studies have continued to explore pembrolizumab combinations:
LEAP-005 study evaluated lenvatinib plus pembrolizumab in previously treated advanced ovarian cancer 4
- Showed 26% objective response rate by investigator assessment
- Demonstrated 21.3 months median overall survival
Case series on pembrolizumab with bevacizumab and cyclophosphamide for recurrent ovarian clear cell carcinoma 5
- All patients receiving pembrolizumab and bevacizumab experienced partial responses
- Responses were durable, ranging from 6 to 15 months
Current Status in Treatment Guidelines
As of 2025, pembrolizumab is not routinely recommended for ovarian cancer treatment in NCCN guidelines 6. Its use is primarily limited to specific biomarker-defined subsets:
- Tumors with microsatellite instability-high (MSI-H) or deficient mismatch repair (dMMR)
- Tumors with high tumor mutational burden (TMB-H)
Research Challenges and Limitations
- Most studies show modest single-agent activity
- Higher efficacy observed in combination therapies
- Potential for significant immune-related adverse events
- Need for better predictive biomarkers beyond PD-L1 expression
The research on pembrolizumab in ovarian cancer continues to evolve, with ongoing trials exploring novel combinations to improve efficacy while managing toxicity profiles.