KEYNOTE-775 / Study 309
After platinum chemotherapy, does lenvatinib plus pembrolizumab improve survival over doxorubicin or paclitaxel?
One underlying study; aliases and follow-up reports consolidated. Primary discipline: Medical.
827 patients with advanced endometrial cancer after platinum-based chemotherapy, including pMMR and dMMR cohorts.
Previously treated advanced/recurrent disease; prior anti-PD-1/PD-L1 treatment was excluded in the trial setting.
827 randomised/evaluable as reported.
Lenvatinib 20 mg orally daily plus pembrolizumab 200 mg IV every 3 weeks (or approved equivalent schedule).
Physician-choice doxorubicin 60 mg/m² every 3 weeks or paclitaxel 80 mg/m² weekly.
Endpoints and results
Co-primary endpoints PFS and OS; response, safety and PROs secondary.
- 5-year OS all-comers 19.9% vs 7.7%; 5-year PFS 9.8% vs 3.2%.
- Updated all-comer HR: OS 0.65 (95% CI 0.55–0.77); PFS 0.56 (95% CI 0.48–0.66).
- Treatment-related AEs led to discontinuation in 32.3% vs 5.9%.
- 5-year OS: pMMR 16.7% vs 7.3%; dMMR 36.5% vs 9.8%.
Absolute Effect and outcome visualisation
5-year OS, all-comers
% alive at 5 years · 5 years. Bars show reported fixed-time percentages.
Interpretation: 5-year OS difference 12.2 percentage points; approximate landmark NNT 9 at 5 years from fixed-time rates, not median OS.
Toxicity, discontinuation and quality of life
Trial-specific harms: Hypertension, diarrhoea, fatigue, hypothyroidism and immune-mediated toxicity; treatment discontinuation 32.3% vs 5.9%.
Treatment burden/discontinuation: Frequent dose interruptions/reductions and monitoring are common; prolonged oral plus IV treatment.
Quality of life: No numerical global QoL advantage claimed here.
Subgroups, maturity and limitations
Subgroups: MMR-specific 5-year OS rates differ substantially; use the reported MMR strata. Prior immunotherapy limits current applicability.
Maturity: Five-year results published in 2026.
Limitations: Trial predates routine first-line checkpoint inhibition for many patients; do not automatically extrapolate after prior immunotherapy.
The combination improves PFS and OS after platinum in the studied population but has substantial toxicity and discontinuation burden.
Current-practice context must be checked against regional guidelines, patient fitness, biomarkers, alternatives and regulatory status before clinical application. Clinical freshness review and browser-rendered QA remain pending.
Primary sources and registry
Registry: NCT03517449
The Absolute Effect · Updated 26 October 2026 · Never derive NNT from median survival.