KEYNOTE-024
Pembrolizumab versus platinum-based chemotherapy as first-line treatment of advanced non-small-cell lung cancer with PD-L1 expression on at least 50% of tumour cells
Phase 3N = 305NCT02142738
- Population
- Previously untreated advanced NSCLC with PD-L1 on at least 50% of tumour cells and no sensitising EGFR mutation or ALK translocation
- Design
- Open-label randomised phase 3 trial. Pembrolizumab 200 mg every 3 weeks (up to 2 years) or investigator's choice of platinum-based chemotherapy (four to six cycles); crossover from chemotherapy to pembrolizumab permitted at progression.
- Primary endpoint
- PFS
- Arms
- Pembrolizumab (experimental, n = 154): Pembrolizumab 200 mg fixed dose every 3 weeks
- Platinum-based chemotherapy (control, n = 151): Investigator's choice of platinum-based chemotherapy
- People
- Reck M, KEYNOTE-024 Investigators
PFSHR 0.50 (95% CI 0.37–0.68)Δ median PFS+4.3 monthsOSHR 0.60 (95% CI 0.41–0.89)Δ 6-month OS+7.8 pointsΔ ORR+17 pointsOSHR 0.63 (95% CI 0.47–0.86)
Show the numbers
| Endpoint | Analysis | Pembrolizumab | Platinum-based chemotherapy | Effect |
|---|---|---|---|---|
| PFSRandomised patients (N = 305)Progression-free survival assessed by blinded, independent, central radiologic review | primaryReck 2016 | median 10.3 months | median 6 months (4.2–6.2) | HR 0.50 (95% CI 0.37–0.68)P<0.001Primary endpoint. The 95% CI for the pembrolizumab median is 6.7 to not reached, so no ci95 is entered for that arm. |
| OSRandomised patients (N = 305) | primaryReck 2016 | 80.2% at 6 mo | 72.4% at 6 mo | HR 0.60 (95% CI 0.41–0.89)P=0.005Overall survival was a secondary endpoint in the primary report. |
| ORRRandomised patients (N = 305) | primaryReck 2016 | 44.8% | 27.8% | Secondary endpoint; no P value or confidence interval for the response rates in the abstract. Grade 3, 4 or 5 treatment-related adverse events: 26.6% vs 53.3%. |
| OSRandomised patients (N = 305) | long term-updatemedian follow-up 25.2 monthsReck 2019 | median 30 months | median 14.2 months (9.8–19.0) | HR 0.63 (95% CI 0.47–0.86)The 95% CI for the pembrolizumab median is 18.3 months to not reached, so no ci95 is entered for that arm. 82 patients assigned to chemotherapy crossed over to pembrolizumab; the crossover-adjusted hazard ratio for OS by the two-stage method was 0.49 (95% CI 0.34 to 0.69), with similar results from two other methods. Treatment-related grade 3 to 5 adverse events: 31.2% vs 53.3%. |
| Endpoint | Analysis | Pembrolizumab | Platinum-based chemotherapy | Effect |
|---|---|---|---|---|
| PFSRandomised patients (N = 305)Progression-free survival assessed by blinded, independent, central radiologic review | primaryReck 2016 | median 10.3 months | median 6 months (4.2–6.2) | HR 0.50 (95% CI 0.37–0.68)P<0.001Primary endpoint. The 95% CI for the pembrolizumab median is 6.7 to not reached, so no ci95 is entered for that arm. |
| OSRandomised patients (N = 305) | primaryReck 2016 | 80.2% at 6 mo | 72.4% at 6 mo | HR 0.60 (95% CI 0.41–0.89)P=0.005Overall survival was a secondary endpoint in the primary report. |
| ORRRandomised patients (N = 305) | primaryReck 2016 | 44.8% | 27.8% | Secondary endpoint; no P value or confidence interval for the response rates in the abstract. Grade 3, 4 or 5 treatment-related adverse events: 26.6% vs 53.3%. |
| OSRandomised patients (N = 305) | long term-updatemedian follow-up 25.2 monthsReck 2019 | median 30 months | median 14.2 months (9.8–19.0) | HR 0.63 (95% CI 0.47–0.86)The 95% CI for the pembrolizumab median is 18.3 months to not reached, so no ci95 is entered for that arm. 82 patients assigned to chemotherapy crossed over to pembrolizumab; the crossover-adjusted hazard ratio for OS by the two-stage method was 0.49 (95% CI 0.34 to 0.69), with similar results from two other methods. Treatment-related grade 3 to 5 adverse events: 31.2% vs 53.3%. |
Data table
| Endpoint | HR | 95% CI |
|---|---|---|
| PFS | 0.5 | 0.37–0.68 |
| OS | 0.6 | 0.41–0.89 |
| OS | 0.63 | 0.47–0.86 |
- Pembrolizumab (experimental)
- Platinum-based chemotherapy (control)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Pembrolizumab | Platinum-based chemotherapy |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 6 | 66.8% | 50.0% |
| 13 | 41.7% | 22.3% |
| 19 | 27.8% | 11.1% |
| 26 | 17.4% | 5.0% |
- Pembrolizumab (experimental)
- Platinum-based chemotherapy (control)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Pembrolizumab | Platinum-based chemotherapy |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 19 | 64.5% | 39.6% |
| 38 | 41.6% | 15.6% |
| 56 | 27.4% | 6.5% |
| 75 | 17.7% | 2.6% |
Appears in
Sources
Reck M, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, et al. Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer. N Engl J Med. 2016;375(19):1823-1833.
Reck M, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, et al. Updated Analysis of KEYNOTE-024: Pembrolizumab Versus Platinum-Based Chemotherapy for Advanced Non-Small-Cell Lung Cancer With PD-L1 Tumor Proportion Score of 50% or Greater. J Clin Oncol. 2019;37(7):537-546.