KEYNOTE-189
Pemetrexed and platinum chemotherapy with or without pembrolizumab as first-line treatment of metastatic nonsquamous non-small-cell lung cancer
Phase 3N = 616NCT02578680
- Population
- Metastatic nonsquamous NSCLC without sensitising EGFR or ALK mutations, no previous treatment for metastatic disease
- Design
- Double-blind randomised phase 3 trial (2:1). Pemetrexed and a platinum-based drug plus pembrolizumab 200 mg or placebo every 3 weeks for 4 cycles, then pembrolizumab or placebo for up to a total of 35 cycles plus pemetrexed maintenance; crossover to pembrolizumab monotherapy permitted for placebo-combination patients with verified disease progression.
- Primary endpoint
- OS, PFS
- Arms
- Pembrolizumab plus pemetrexed-platinum (experimental, n = 410): Pembrolizumab 200 mg every 3 weeks plus pemetrexed and platinum for 4 cycles, then pembrolizumab (up to 35 cycles) and pemetrexed maintenance
- Placebo plus pemetrexed-platinum (control, n = 206): Placebo plus pemetrexed and platinum for 4 cycles, then placebo and pemetrexed maintenance
- People
- Gandhi L, KEYNOTE-189 Investigators
OSHR 0.49 (95% CI 0.38–0.64)Δ 12-month OS+19.8 pointsPFSHR 0.52 (95% CI 0.43–0.64)Δ median PFS+3.9 monthsOSHR 0.56 (95% CI 0.45–0.70)Δ median OS+11.3 months
Show the numbers
| Endpoint | Analysis | Pembrolizumab plus pemetrexed-platinum | Placebo plus pemetrexed-platinum | Effect |
|---|---|---|---|---|
| OSRandomised patients (N = 616) | primarymedian follow-up 10.5 monthsGandhi 2018 | 69.2% at 12 mo (64.1–73.8%) | 49.4% at 12 mo (42.1–56.2%) | HR 0.49 (95% CI 0.38–0.64)P<0.001Primary endpoint (with PFS). The first report gives no median OS in the abstract. |
| PFSRandomised patients (N = 616)Progression-free survival assessed by blinded, independent central radiologic review | primarymedian follow-up 10.5 monthsGandhi 2018 | median 8.8 months (7.6–9.2) | median 4.9 months (4.7–5.5) | HR 0.52 (95% CI 0.43–0.64)P<0.001Grade 3 or higher adverse events: 67.2% (pembrolizumab combination) vs 65.8% (placebo combination). |
| OSRandomised patients (N = 616) | long term-updatemedian follow-up 23.1 monthsGadgeel 2020 | median 22 months (19.5–25.2) | median 10.7 months (8.7–13.6) | HR 0.56 (95% CI 0.45–0.70)No alpha was assigned to this updated analysis (as stated in the abstract). |
| PFSRandomised patients (N = 616) | long term-updatemedian follow-up 23.1 monthsGadgeel 2020 | median 9 months (8.1–9.9) | median 4.9 months (4.7–5.5) | HR 0.48 (95% CI 0.40–0.58)No alpha was assigned to this updated analysis. |
| OSRandomised patients (N = 616) | long term-updatemedian follow-up 64.6 monthsGarassino 2023 | 19.4% at 5 y | 11.3% at 5 y | HR 0.60 (95% CI 0.50–0.72)The 64.6 months (range 60.1 to 72.4) is the median time from random assignment to data cutoff, as the abstract words it. The abstract gives a PFS hazard ratio of 0.50 (95% CI 0.42 to 0.60) and no medians or confidence intervals for the 5-year rates. |
| Endpoint | Analysis | Pembrolizumab plus pemetrexed-platinum | Placebo plus pemetrexed-platinum | Effect |
|---|---|---|---|---|
| OSRandomised patients (N = 616) | primarymedian follow-up 10.5 monthsGandhi 2018 | 69.2% at 12 mo (64.1–73.8%) | 49.4% at 12 mo (42.1–56.2%) | HR 0.49 (95% CI 0.38–0.64)P<0.001Primary endpoint (with PFS). The first report gives no median OS in the abstract. |
| PFSRandomised patients (N = 616)Progression-free survival assessed by blinded, independent central radiologic review | primarymedian follow-up 10.5 monthsGandhi 2018 | median 8.8 months (7.6–9.2) | median 4.9 months (4.7–5.5) | HR 0.52 (95% CI 0.43–0.64)P<0.001Grade 3 or higher adverse events: 67.2% (pembrolizumab combination) vs 65.8% (placebo combination). |
| OSRandomised patients (N = 616) | long term-updatemedian follow-up 23.1 monthsGadgeel 2020 | median 22 months (19.5–25.2) | median 10.7 months (8.7–13.6) | HR 0.56 (95% CI 0.45–0.70)No alpha was assigned to this updated analysis (as stated in the abstract). |
| PFSRandomised patients (N = 616) | long term-updatemedian follow-up 23.1 monthsGadgeel 2020 | median 9 months (8.1–9.9) | median 4.9 months (4.7–5.5) | HR 0.48 (95% CI 0.40–0.58)No alpha was assigned to this updated analysis. |
| OSRandomised patients (N = 616) | long term-updatemedian follow-up 64.6 monthsGarassino 2023 | 19.4% at 5 y | 11.3% at 5 y | HR 0.60 (95% CI 0.50–0.72)The 64.6 months (range 60.1 to 72.4) is the median time from random assignment to data cutoff, as the abstract words it. The abstract gives a PFS hazard ratio of 0.50 (95% CI 0.42 to 0.60) and no medians or confidence intervals for the 5-year rates. |
Data table
| Endpoint | HR | 95% CI |
|---|---|---|
| OS | 0.49 | 0.38–0.64 |
| PFS | 0.52 | 0.43–0.64 |
| OS | 0.56 | 0.45–0.7 |
| PFS | 0.48 | 0.4–0.58 |
| OS | 0.6 | 0.5–0.72 |
- Pembrolizumab plus pemetrexed-platinum (experimental)
- Placebo plus pemetrexed-platinum (control)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Pembrolizumab plus pemetrexed-platinum | Placebo plus pemetrexed-platinum |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 6 | 62.3% | 42.8% |
| 11 | 42.0% | 21.1% |
| 17 | 26.2% | 9.0% |
| 22 | 17.7% | 4.5% |
- Pembrolizumab plus pemetrexed-platinum (experimental)
- Placebo plus pemetrexed-platinum (control)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Pembrolizumab plus pemetrexed-platinum | Placebo plus pemetrexed-platinum |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 14 | 64.3% | 40.4% |
| 28 | 41.4% | 16.3% |
| 41 | 27.5% | 7.0% |
| 55 | 17.7% | 2.8% |
Appears in
Sources
Gandhi L, Rodríguez-Abreu D, Gadgeel S, Esteban E, Felip E, De Angelis F, et al. Pembrolizumab plus Chemotherapy in Metastatic Non-Small-Cell Lung Cancer. N Engl J Med. 2018;378(22):2078-2092.
Gadgeel S, Rodríguez-Abreu D, Speranza G, Esteban E, Felip E, Dómine M, et al. Updated Analysis From KEYNOTE-189: Pembrolizumab or Placebo Plus Pemetrexed and Platinum for Previously Untreated Metastatic Nonsquamous Non-Small-Cell Lung Cancer. J Clin Oncol. 2020;38(14):1505-1517.
Garassino MC, Gadgeel S, Speranza G, Felip E, Esteban E, Dómine M, et al. Pembrolizumab Plus Pemetrexed and Platinum in Nonsquamous Non-Small-Cell Lung Cancer: 5-Year Outcomes From the Phase 3 KEYNOTE-189 Study. J Clin Oncol. 2023;41(11):1992-1998.