The Absolute Effect / Evidence / KEYNOTE-045
Bladder Cancer · Medical · Advanced / metastatic second line
KEYNOTE-045
Clinical question
After platinum-based chemotherapy, does pembrolizumab improve survival compared with investigator-choice chemotherapy in advanced urothelial carcinoma?
Trial context
Population
542 patients
Intervention
Pembrolizumab 200 mg IV q3w; control paclitaxel 175 mg/m², docetaxel 75 mg/m² or vinflunine 320 mg/m² q3w.
Comparator
Investigator-choice chemotherapy
Primary / key evidence
Median OS 10.3 vs 7.4 mo; HR 0.73; P=.002. Median PFS 2.1 vs 3.3 mo; HR 0.98. Grade ≥3 treatment-related AEs 15.0% vs 49.4%.
Absolute Effect
What changes for patients?
Median OS 10.3 vs 7.4 mo; HR 0.73; P=.002. Median PFS 2.1 vs 3.3 mo; HR 0.98. Grade ≥3 treatment-related AEs 15.0% vs 49.4%.
NNT/NNH: Not calculated unless a defensible fixed-time event-rate comparison was available in the cited primary analysis; median-survival differences alone are not converted to NNT.
Clinical interpretation
Pembrolizumab improved OS despite no significant PFS advantage and had substantially fewer grade ≥3 treatment-related adverse events.
Limitations / maturity
Interpret the effect in the context of the trial population, endpoint definition, follow-up and treatment era. Subsequent trials and evolving standards may limit direct applicability to contemporary patients.
Primary publication
Bellmunt J et al. N Engl J Med. 2017;376:1015–1026.