KEYNOTE-A18
Pembrolizumab or placebo with chemoradiotherapy followed by pembrolizumab or placebo for newly diagnosed, high-risk, locally advanced cervical cancer (ENGOT-cx11/GOG-3047/KEYNOTE-A18)
Phase 3N = 1,060NCT04221945
- Population
- Adults with newly diagnosed, high-risk (FIGO 2014 stage IB2-IIB with node-positive disease, or stage III-IVA regardless of nodal status), locally advanced, histologically confirmed squamous cell carcinoma, adenocarcinoma or adenosquamous cervical cancer
- Design
- Randomised (1:1), double-blind, placebo-controlled phase 3 trial at 176 medical centres in 30 countries: five cycles of pembrolizumab 200 mg or placebo every 3 weeks with chemoradiotherapy, then 15 cycles of pembrolizumab 400 mg or placebo every 6 weeks. Stratified by planned external-beam radiotherapy type, FIGO 2014 stage (IB2-IIB node positive vs III-IVA) and planned total radiotherapy dose. Registry lists 1060 participants, matching the paper.
- Primary endpoint
- PFS, OS
- Arms
- Pembrolizumab with chemoradiotherapy (experimental, n = 529): Pembrolizumab 200 mg every 3 weeks for five cycles with chemoradiotherapy, then pembrolizumab 400 mg every 6 weeks for 15 cycles
- Placebo with chemoradiotherapy (control, n = 531): Placebo every 3 weeks for five cycles with chemoradiotherapy, then placebo every 6 weeks for 15 cycles
- People
- Lorusso D, ENGOT-cx11/GOG-3047/KEYNOTE-A18
PFSHR 0.70 (95% CI 0.55–0.89)Δ 24-month PFS+11 pointsOSHR 0.73 (95% CI 0.49–1.07)Δ 24-month OS+6 pointsOSHR 0.67 (95% CI 0.5–0.9)Δ 36-month OS+7.8 points
Show the numbers
| Endpoint | Analysis | Pembrolizumab with chemoradiotherapy | Placebo with chemoradiotherapy | Effect |
|---|---|---|---|---|
| PFSITT (all randomly allocated participants) | interimmedian follow-up 17.9 monthsLorusso 2024 | 68% at 2 y | 57% at 2 y | HR 0.70 (95% CI 0.55–0.89)P=0.0020First interim analysis; the abstract states the hazard ratio met the protocol-specified primary objective. PFS per RECIST 1.1 by investigator or histopathological confirmation; median not reached in either group. Grade 3 or higher adverse events: 75% with pembrolizumab versus 69% with placebo. |
| OSITT (all randomly allocated participants) | interimmedian follow-up 17.9 monthsLorusso 2024 | 87% at 2 y | 81% at 2 y | HR 0.73 (95% CI 0.49–1.07)First interim analysis (information fraction 42.9%); the abstract states these data have not crossed the boundary of statistical significance. |
| OSRandomly assigned participants (1060); the abstract does not name the analysis population | interimmedian follow-up 29.9 monthsLorusso 2024 | 82.6% at 3 y (78.4–86.1%) | 74.8% at 3 y (70.1–78.8%) | HR 0.67 (95% CI 0.5–0.9)P=0.0040Protocol-specified second interim analysis; median overall survival not reached in either group. Grade 3 or higher adverse events: 413 of 528 (78%) with pembrolizumab versus 371 of 530 (70%) with placebo; potentially immune-mediated adverse events in 206 (39%) versus 90 (17%). |
| Endpoint | Analysis | Pembrolizumab with chemoradiotherapy | Placebo with chemoradiotherapy | Effect |
|---|---|---|---|---|
| PFSITT (all randomly allocated participants) | interimmedian follow-up 17.9 monthsLorusso 2024 | 68% at 2 y | 57% at 2 y | HR 0.70 (95% CI 0.55–0.89)P=0.0020First interim analysis; the abstract states the hazard ratio met the protocol-specified primary objective. PFS per RECIST 1.1 by investigator or histopathological confirmation; median not reached in either group. Grade 3 or higher adverse events: 75% with pembrolizumab versus 69% with placebo. |
| OSITT (all randomly allocated participants) | interimmedian follow-up 17.9 monthsLorusso 2024 | 87% at 2 y | 81% at 2 y | HR 0.73 (95% CI 0.49–1.07)First interim analysis (information fraction 42.9%); the abstract states these data have not crossed the boundary of statistical significance. |
| OSRandomly assigned participants (1060); the abstract does not name the analysis population | interimmedian follow-up 29.9 monthsLorusso 2024 | 82.6% at 3 y (78.4–86.1%) | 74.8% at 3 y (70.1–78.8%) | HR 0.67 (95% CI 0.5–0.9)P=0.0040Protocol-specified second interim analysis; median overall survival not reached in either group. Grade 3 or higher adverse events: 413 of 528 (78%) with pembrolizumab versus 371 of 530 (70%) with placebo; potentially immune-mediated adverse events in 206 (39%) versus 90 (17%). |
Data table
| Endpoint | HR | 95% CI |
|---|---|---|
| PFS | 0.7 | 0.55–0.89 |
| OS | 0.73 | 0.49–1.07 |
| OS | 0.67 | 0.5–0.9 |
Appears in
Sources
Lorusso D, Xiang Y, Hasegawa K, Scambia G, Leiva M, Ramos-Elias P, et al. Pembrolizumab or placebo with chemoradiotherapy followed by pembrolizumab or placebo for newly diagnosed, high-risk, locally advanced cervical cancer (ENGOT-cx11/GOG-3047/KEYNOTE-A18): a randomised, double-blind, phase 3 clinical trial. Lancet. 2024;403(10434):1341-1350.
Lorusso D, Xiang Y, Hasegawa K, Scambia G, Leiva M, Ramos-Elias P, et al. Pembrolizumab or placebo with chemoradiotherapy followed by pembrolizumab or placebo for newly diagnosed, high-risk, locally advanced cervical cancer (ENGOT-cx11/GOG-3047/KEYNOTE-A18): overall survival results from a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2024;404(10460):1321-1332.