- Pembrolizumab extended OS vs chemotherapy when used as second-line (2L) therapy for advanced esophageal cancer in patients with a PD-L1 combined positive score (CPS) ≥10.
Why this matters
- Chemotherapy is currently used despite its failure to show survival benefit in this population.
- Findings support pembrolizumab as a new standard of care.
- KEYNOTE-181 phase 3 open-label study of 628 patients with advanced esophageal cancer that had progressed after first-line chemotherapy, randomly assigned to 200 mg pembrolizumab once every 3 weeks for up to 2 years, or investigator’s choice of paclitaxel, docetaxel or irinotecan.
- Patients were stratified by histology (squamous cell carcinoma (SCC) vs adenocarcinoma) and region (Asia vs rest of the world)
- 222 with PD-L1 CPS ≥10, 401 with SCC
- Funding: MSD.
- Median follow-up: 7.1 months with pembrolizumab, 6.9 months with chemotherapy.
- In PD-L1 CPS ≥10 tumors: OS was 9.3 months for pembrolizumab vs 6.9 months for chemotherapy (P=0.0074; HR 0.69)
- Pembrolizumab OS advantage was not statistically significant in squamous cell carcinoma (SCC) or the overall intent-to-treat (ITT) population.
- Lack of stratification by PD-L1 status, raising the possibility that benefit in the PD-L1 CPS > 10 subgroup was due to a high frequency of favorable prognostic variables rather than pembrolizumab.