The Absolute Effect / Evidence / EV-302 / KEYNOTE-A39
Bladder Cancer · Medical · Locally advanced / metastatic first line
EV-302 / KEYNOTE-A39
Clinical question
In untreated locally advanced or metastatic urothelial carcinoma, does enfortumab vedotin plus pembrolizumab improve outcomes over platinum-gemcitabine chemotherapy?
Trial context
Population
886 patients
Intervention
Enfortumab vedotin 1.25 mg/kg IV days 1 and 8 q21d + pembrolizumab 200 mg IV q3w; control gemcitabine + cisplatin or carboplatin.
Comparator
Platinum + gemcitabine
Primary / key evidence
Median OS 31.5 vs 16.1 mo; HR 0.47. Median PFS 12.5 vs 6.3 mo; HR 0.45. ORR 67.7% vs 44.4%.
Absolute Effect
What changes for patients?
Median OS 31.5 vs 16.1 mo; HR 0.47. Median PFS 12.5 vs 6.3 mo; HR 0.45. ORR 67.7% vs 44.4%.
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
The combination produced large improvements in both PFS and OS versus platinum-gemcitabine in previously untreated advanced urothelial cancer.
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
Powles T et al. N Engl J Med. 2024;390:875–888.