This retrospective real-world study examined whether pretreatment tumor NECTIN4 RNA expression and tumor mutational burden (TMB) predict outcomes in metastatic urothelial carcinoma (mUC) patients receiving first-line enfortumab vedotin + pembrolizumab (EV+P; N=322) versus pembrolizumab monotherapy (N=232).
NECTIN4-high tumors independently predicted better OS (adjusted HR 0.62; median 21.5 vs 14.2 months) and higher ORR (67.4% vs 41.9%) with EV+P; combining NECTIN4-high and/or TMB-high further enriched for response (OR 3.09), while NECTIN4-low/TMB-low patients had the worst outcomes. NECTIN4 was not significantly predictive in the pembrolizumab monotherapy cohort.
Retrospective, real-world design introduces selection bias and unmeasured confounding; NECTIN4 cutoffs and TMB thresholds require prospective validation; the pembrolizumab monotherapy comparator cohort may differ in baseline characteristics.
Consider testing pretreatment tumor NECTIN4 RNA expression and TMB in mUC patients starting EV+P — NECTIN4-low/TMB-low patients have the lowest chance of response and may need alternative or intensified strategies, though prospective validation is still needed.
Explore related topics
