KEYNOTE-062
Study of Pembrolizumab (MK-3475) as First-Line Monotherapy and Combination Therapy for Treatment of Advanced Gastric or Gastroesophageal Junction Adenocarcinoma (MK-3475-062/KEYNOTE-062)
Phase 3N = 763NCT02494583
- Population
- Untreated locally advanced/unresectable or metastatic gastric or gastro-oesophageal junction cancer with PD-L1 CPS of 1 or more.
- Design
- Randomised, controlled, partially blinded phase 3 trial at 200 centres in 29 countries. 763 patients were randomised 1:1:1 to pembrolizumab 200 mg, pembrolizumab plus chemotherapy (cisplatin plus fluorouracil or capecitabine) or chemotherapy plus placebo, every 3 weeks. Primary endpoints: overall survival and progression-free survival in patients with PD-L1 CPS 1 or more or 10 or more. Final analysis, median follow-up 29.4 months.
- Primary endpoint
- OS, PFS
- Arms
- Chemotherapy plus placebo (control, n = 250): Cisplatin plus fluorouracil or capecitabine with placebo
- Pembrolizumab (experimental, n = 256): Pembrolizumab 200 mg every 3 weeks
- Pembrolizumab plus chemotherapy (experimental, n = 257): Pembrolizumab 200 mg every 3 weeks with cisplatin plus fluorouracil or capecitabine
- People
- Shitara K, senior author Tabernero J
OSHR 0.91Δ median OS−0.5 monthsOSHR 0.69 (95% CI 0.49–0.97)Δ median OS+6.6 monthsOSHR 0.85 (95% CI 0.70–1.03)Δ median OS+1.4 months
Show the numbers
| Endpoint | Analysis | Pembrolizumab / Pembrolizumab plus chemotherapy | Chemotherapy plus placebo | Effect |
|---|---|---|---|---|
| OSPD-L1 CPS 1 or more | finalShitara 2020 | median 10.6 months | median 11.1 months | HR 0.91Noninferiority comparison reported in the abstract; the hazard ratio is given with a 99.2% confidence interval of 0.69 to 1.18 (not a 95% interval). The abstract states pembrolizumab was noninferior but not superior to chemotherapy. |
| OSPD-L1 CPS 10 or more | exploratoryShitara 2020 | median 17.4 months | median 10.8 months | HR 0.69 (95% CI 0.49–0.97)The abstract states this difference was not statistically tested. |
| OSPD-L1 CPS 1 or more | finalShitara 2020 | median 12.5 months | median 11.1 months | HR 0.85 (95% CI 0.70–1.03)P=.05The abstract states pembrolizumab plus chemotherapy was not superior to chemotherapy for OS in patients with CPS 1 or more. |
| Endpoint | Analysis | Pembrolizumab / Pembrolizumab plus chemotherapy | Chemotherapy plus placebo | Effect |
|---|---|---|---|---|
| OSPD-L1 CPS 1 or more | finalShitara 2020 | median 10.6 months | median 11.1 months | HR 0.91Noninferiority comparison reported in the abstract; the hazard ratio is given with a 99.2% confidence interval of 0.69 to 1.18 (not a 95% interval). The abstract states pembrolizumab was noninferior but not superior to chemotherapy. |
| OSPD-L1 CPS 10 or more | exploratoryShitara 2020 | median 17.4 months | median 10.8 months | HR 0.69 (95% CI 0.49–0.97)The abstract states this difference was not statistically tested. |
| OSPD-L1 CPS 1 or more | finalShitara 2020 | median 12.5 months | median 11.1 months | HR 0.85 (95% CI 0.70–1.03)P=.05The abstract states pembrolizumab plus chemotherapy was not superior to chemotherapy for OS in patients with CPS 1 or more. |
Data table
| Endpoint | HR | 95% CI |
|---|---|---|
| OS | 0.69 | 0.49–0.97 |
| OS | 0.85 | 0.7–1.03 |
- Pembrolizumab (experimental)
- Chemotherapy plus placebo (control)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Pembrolizumab | Chemotherapy plus placebo |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 7 | 63.3% | 64.6% |
| 14 | 40.0% | 41.7% |
| 21 | 25.3% | 26.9% |
| 28 | 16.0% | 17.4% |
- Pembrolizumab (experimental)
- Chemotherapy plus placebo (control)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Pembrolizumab | Chemotherapy plus placebo |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 11 | 64.5% | 49.4% |
| 22 | 41.6% | 24.4% |
| 33 | 26.9% | 12.0% |
| 44 | 17.3% | 5.9% |
Appears in
Sources
Shitara K, Van Cutsem E, Bang YJ, Fuchs C, Wyrwicz L, Lee KW, et al. Efficacy and Safety of Pembrolizumab or Pembrolizumab Plus Chemotherapy vs Chemotherapy Alone for Patients With First-line, Advanced Gastric Cancer: The KEYNOTE-062 Phase 3 Randomized Clinical Trial. JAMA Oncol. 2020;6(10):1571-1580.