KEYNOTE-407
Carboplatin and paclitaxel or nab-paclitaxel with or without pembrolizumab as first-line treatment of metastatic squamous non-small-cell lung cancer
Phase 3N = 559NCT02775435
- Population
- Untreated metastatic squamous NSCLC
- Design
- Double-blind randomised phase 3 trial (1:1). Pembrolizumab 200 mg or saline placebo for up to 35 cycles; all patients also received carboplatin and either paclitaxel or nanoparticle albumin-bound (nab) paclitaxel for the first 4 cycles.
- Primary endpoint
- OS, PFS
- Arms
- Pembrolizumab plus carboplatin and paclitaxel or nab-paclitaxel (experimental): Pembrolizumab 200 mg for up to 35 cycles plus carboplatin and paclitaxel or nab-paclitaxel for the first 4 cycles
- Placebo plus carboplatin and paclitaxel or nab-paclitaxel (control): Saline placebo plus carboplatin and paclitaxel or nab-paclitaxel for the first 4 cycles
- People
- Paz-Ares L, KEYNOTE-407 Investigators
OSHR 0.64 (95% CI 0.49–0.85)Δ median OS+4.6 monthsPFSHR 0.56 (95% CI 0.45–0.70)Δ median PFS+1.6 months
Show the numbers
| Endpoint | Analysis | Pembrolizumab plus carboplatin and paclitaxel or nab-paclitaxel | Placebo plus carboplatin and paclitaxel or nab-paclitaxel | Effect |
|---|---|---|---|---|
| OSRandomised patients (N = 559) | primarymedian follow-up 7.8 monthsPaz-Ares 2018 | median 15.9 months | median 11.3 months (9.5–14.8) | HR 0.64 (95% CI 0.49–0.85)P<0.001The 95% CI for the pembrolizumab-combination median is 13.2 to not reached, so no ci95 is entered for that arm. The abstract states the OS benefit was consistent regardless of PD-L1 expression. |
| PFSRandomised patients (N = 559) | primarymedian follow-up 7.8 monthsPaz-Ares 2018 | median 6.4 months (6.2–8.3) | median 4.8 months (4.3–5.7) | HR 0.56 (95% CI 0.45–0.70)P<0.001Grade 3 or higher adverse events: 69.8% (pembrolizumab combination) vs 68.2% (placebo combination). |
| Endpoint | Analysis | Pembrolizumab plus carboplatin and paclitaxel or nab-paclitaxel | Placebo plus carboplatin and paclitaxel or nab-paclitaxel | Effect |
|---|---|---|---|---|
| OSRandomised patients (N = 559) | primarymedian follow-up 7.8 monthsPaz-Ares 2018 | median 15.9 months | median 11.3 months (9.5–14.8) | HR 0.64 (95% CI 0.49–0.85)P<0.001The 95% CI for the pembrolizumab-combination median is 13.2 to not reached, so no ci95 is entered for that arm. The abstract states the OS benefit was consistent regardless of PD-L1 expression. |
| PFSRandomised patients (N = 559) | primarymedian follow-up 7.8 monthsPaz-Ares 2018 | median 6.4 months (6.2–8.3) | median 4.8 months (4.3–5.7) | HR 0.56 (95% CI 0.45–0.70)P<0.001Grade 3 or higher adverse events: 69.8% (pembrolizumab combination) vs 68.2% (placebo combination). |
Data table
| Endpoint | HR | 95% CI |
|---|---|---|
| OS | 0.64 | 0.49–0.85 |
| PFS | 0.56 | 0.45–0.7 |
- Pembrolizumab plus carboplatin and paclitaxel or nab-paclitaxel (experimental)
- Placebo plus carboplatin and paclitaxel or nab-paclitaxel (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 carboplatin and paclitaxel or nab-paclitaxel | Placebo plus carboplatin and paclitaxel or nab-paclitaxel |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 10 | 64.7% | 54.2% |
| 20 | 41.8% | 29.3% |
| 30 | 27.0% | 15.9% |
| 40 | 17.5% | 8.6% |
- Pembrolizumab plus carboplatin and paclitaxel or nab-paclitaxel (experimental)
- Placebo plus carboplatin and paclitaxel or nab-paclitaxel (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 carboplatin and paclitaxel or nab-paclitaxel | Placebo plus carboplatin and paclitaxel or nab-paclitaxel |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 4 | 64.8% | 56.1% |
| 8 | 42.0% | 31.5% |
| 12 | 27.3% | 17.7% |
| 16 | 17.7% | 9.9% |