KEYNOTE-001 (Garon 2015): pembrolizumab in non-small-cell lung cancer and the 50% PD-L1 cut-off
The large early trial that showed pembrolizumab shrinks about a fifth of advanced lung cancers, with responses that last, and that identified a PD-L1 score of 50% or more as the group most likely to benefit.
Overview
KEYNOTE-001 treated 495 patients with advanced non-small-cell lung cancer, both previously treated and untreated, with pembrolizumab at several doses and schedules. The overall response rate was about 19% with a median duration of response around a year and no clear difference between doses. A training and validation approach on PD-L1 immunohistochemistry defined a tumour proportion score of at least 50% as the threshold at which response and survival were markedly better, a cut-off adopted by KEYNOTE-024 and now used in clinics worldwide.
- 495 patients with advanced NSCLC treated with pembrolizumab at 2 or 10 mg/kg every three weeks or 10 mg/kg every two weeks.
- Objective response rate 19.4% overall; median duration of response 12.5 months.
- PD-L1 tumour proportion score of at least 50%, seen in 23.2% of patients, was associated with a response rate of 45.2% and longer progression-free and overall survival.
- Treatment-related grade 3 or higher adverse events in 9.5% of patients.
This trial gave lung cancer its immunotherapy biomarker. The 50% PD-L1 cut-off decides today whether a patient with advanced lung cancer can start immunotherapy alone or needs chemotherapy added, and the five-year follow-up later showed long-term survivors among first-line responders.
- Single-arm study with several dose cohorts; the cut-off was derived and validated within the same trial.
- PD-L1 testing depends on the assay and the sample and misses some responders.
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