KEYNOTE-671
Perioperative pembrolizumab with cisplatin-based chemotherapy versus placebo with chemotherapy in resectable early-stage non-small-cell lung cancer
Phase 3N = 797NCT03425643
- Population
- Resectable stage II, IIIA or IIIB (N2) non-small-cell lung cancer
- Design
- Randomised (1:1), double-blind phase 3 trial. Neoadjuvant pembrolizumab 200 mg or placebo every 3 weeks with cisplatin-based chemotherapy for 4 cycles, then surgery, then adjuvant pembrolizumab 200 mg or placebo every 3 weeks for up to 13 cycles.
- Primary endpoint
- EFS, OS
- Arms
- Pembrolizumab plus chemotherapy (experimental, n = 397): Neoadjuvant pembrolizumab 200 mg plus cisplatin-based chemotherapy for 4 cycles, surgery, then adjuvant pembrolizumab for up to 13 cycles
- Placebo plus chemotherapy (control, n = 400): Neoadjuvant placebo plus cisplatin-based chemotherapy for 4 cycles, surgery, then adjuvant placebo for up to 13 cycles
- People
- Wakelee H, KEYNOTE-671 Investigators
EFSHR 0.58 (95% CI 0.46–0.72)Δ 24-month EFS+21.8 pointsΔ 24-month OS+3.3 pointsΔ MPR+19.2 pointsΔ pCR+14.1 pointsOSHR 0.72 (95% CI 0.56–0.93)
Show the numbers
| Endpoint | Analysis | Pembrolizumab plus chemotherapy | Placebo plus chemotherapy | Effect |
|---|---|---|---|---|
| EFSITT (all randomised participants, N = 797)Time from randomization to local progression precluding the planned surgery, unresectable tumour, progression or recurrence, or death | interimmedian follow-up 25.2 monthsWakelee 2023 | 62.4% at 2 y | 40.6% at 2 y | HR 0.58 (95% CI 0.46–0.72)P<0.001Dual primary endpoint. |
| OSITT (all randomised participants, N = 797) | interimmedian follow-up 25.2 monthsWakelee 2023 | 80.9% at 2 y | 77.6% at 2 y | P=0.02Dual primary endpoint. The abstract states P=0.02 did not meet the significance criterion at this first interim analysis. |
| MPRITT (all randomised participants, N = 797) | interimWakelee 2023 | 30.2% | 11% | P<0.0001Secondary endpoint. Difference 19.2 percentage points (95% CI 13.9 to 24.7); threshold P=0.0001. |
| pCRITT (all randomised participants, N = 797) | interimWakelee 2023 | 18.1% | 4% | P<0.0001Secondary endpoint. Difference 14.2 percentage points (95% CI 10.1 to 18.7); threshold P=0.0001. Grade 3 or higher treatment-related adverse events across all phases: 44.9% vs 37.3%. |
| OSIntention-to-treat (all randomised participants) | interimmedian follow-up 36.6 monthsSpicer 2024 | 71% at 3 y (66–76%) | 64% at 3 y (58–69%) | HR 0.72 (95% CI 0.56–0.93)P=0.0052 (one-sided; threshold 0.0054)Dual primary endpoint. Median study follow-up 36.6 months at the second interim analysis. |
| EFSIntention-to-treat (all randomised participants) | interimmedian follow-up 36.6 monthsSpicer 2024 | median 47.2 months | median 18.3 months (14.8–22.1) | HR 0.59 (95% CI 0.48–0.72)The 95% CI for the pembrolizumab median is 32.9 to not reached, so no ci95 is entered for that arm. |
| EFSRandomised participants (N = 797)Event-free survival per RECIST v1.1 by investigator assessment | long term-updatemedian follow-up 60.4 monthsWakelee 2026 | 49.9% at 5 y (44.6–55.0%) | 26.5% at 5 y (21.7–31.5%) | HR 0.58 (95% CI 0.48–0.69)The 60.4 months (range 42.6 to 85.8) is the median time from randomization to data cutoff, as the abstract words it. |
| OSRandomised participants (N = 797) | long term-updatemedian follow-up 60.4 monthsWakelee 2026 | 64.6% at 5 y (59.5–69.2%) | 53.6% at 5 y (48.3–58.6%) | HR 0.74 (95% CI 0.59–0.92) |
| Endpoint | Analysis | Pembrolizumab plus chemotherapy | Placebo plus chemotherapy | Effect |
|---|---|---|---|---|
| EFSITT (all randomised participants, N = 797)Time from randomization to local progression precluding the planned surgery, unresectable tumour, progression or recurrence, or death | interimmedian follow-up 25.2 monthsWakelee 2023 | 62.4% at 2 y | 40.6% at 2 y | HR 0.58 (95% CI 0.46–0.72)P<0.001Dual primary endpoint. |
| OSITT (all randomised participants, N = 797) | interimmedian follow-up 25.2 monthsWakelee 2023 | 80.9% at 2 y | 77.6% at 2 y | P=0.02Dual primary endpoint. The abstract states P=0.02 did not meet the significance criterion at this first interim analysis. |
| MPRITT (all randomised participants, N = 797) | interimWakelee 2023 | 30.2% | 11% | P<0.0001Secondary endpoint. Difference 19.2 percentage points (95% CI 13.9 to 24.7); threshold P=0.0001. |
| pCRITT (all randomised participants, N = 797) | interimWakelee 2023 | 18.1% | 4% | P<0.0001Secondary endpoint. Difference 14.2 percentage points (95% CI 10.1 to 18.7); threshold P=0.0001. Grade 3 or higher treatment-related adverse events across all phases: 44.9% vs 37.3%. |
| OSIntention-to-treat (all randomised participants) | interimmedian follow-up 36.6 monthsSpicer 2024 | 71% at 3 y (66–76%) | 64% at 3 y (58–69%) | HR 0.72 (95% CI 0.56–0.93)P=0.0052 (one-sided; threshold 0.0054)Dual primary endpoint. Median study follow-up 36.6 months at the second interim analysis. |
| EFSIntention-to-treat (all randomised participants) | interimmedian follow-up 36.6 monthsSpicer 2024 | median 47.2 months | median 18.3 months (14.8–22.1) | HR 0.59 (95% CI 0.48–0.72)The 95% CI for the pembrolizumab median is 32.9 to not reached, so no ci95 is entered for that arm. |
| EFSRandomised participants (N = 797)Event-free survival per RECIST v1.1 by investigator assessment | long term-updatemedian follow-up 60.4 monthsWakelee 2026 | 49.9% at 5 y (44.6–55.0%) | 26.5% at 5 y (21.7–31.5%) | HR 0.58 (95% CI 0.48–0.69)The 60.4 months (range 42.6 to 85.8) is the median time from randomization to data cutoff, as the abstract words it. |
| OSRandomised participants (N = 797) | long term-updatemedian follow-up 60.4 monthsWakelee 2026 | 64.6% at 5 y (59.5–69.2%) | 53.6% at 5 y (48.3–58.6%) | HR 0.74 (95% CI 0.59–0.92) |
Data table
| Endpoint | HR | 95% CI |
|---|---|---|
| EFS | 0.58 | 0.46–0.72 |
| OS | 0.72 | 0.56–0.93 |
| EFS | 0.59 | 0.48–0.72 |
| EFS | 0.58 | 0.48–0.69 |
| OS | 0.74 | 0.59–0.92 |
- Pembrolizumab plus chemotherapy (experimental)
- Placebo plus 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 plus chemotherapy | Placebo plus chemotherapy |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 30 | 64.4% | 32.1% |
| 59 | 42.0% | 10.7% |
| 89 | 27.1% | 3.4% |
| 118 | 17.7% | 1.1% |
Appears in
Sources
Wakelee H, Liberman M, Kato T, Tsuboi M, Lee SH, Gao S, et al. Perioperative Pembrolizumab for Early-Stage Non-Small-Cell Lung Cancer. N Engl J Med. 2023;389(6):491-503.
Spicer JD, Garassino MC, Wakelee H, Liberman M, Kato T, Tsuboi M, et al. Neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab compared with neoadjuvant chemotherapy alone in patients with early-stage non-small-cell lung cancer (KEYNOTE-671): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2024;404(10459):1240-1252.
Wakelee H, Spicer JD, Gao S, Liberman M, Tsuboi M, Kato T, et al. Five-Year Outcomes of Perioperative Pembrolizumab for Early-Stage Non-Small-Cell Lung Cancer From the Randomized KEYNOTE-671 Study. Ann Oncol. 2026;.