Erdafitinib or Erdafitinib Plus Cetrelimab for Patients With Metastatic Urothelial Carcinoma and FGFR Alterations: Final Results From the Phase II NORSE Study
Mené sur 87 patients atteints d'un carcinome urothélial métastatique avec altération du gène FGFR (durée médiane de suivi : 14,2 mois), cet essai randomisé de phase II évalue l'efficacité, du point de vue du taux de réponse globale, et la toxicité de l'erdafitinib avec ou sans cétrélimab, en traitement de première ligne
Purpose: First-line treatment options for cisplatin-ineligible patients with metastatic urothelial cancer (mUC) are limited. We conducted a phase II study of erdafitinib, alone or with cetrelimab, in FGFR-altered mUC.
Methods: Adults with mUC and select FGFR alterations who are ineligible for cisplatin were randomly assigned 1:1 in a noncomparative design to once-daily erdafitinib 8 mg (with pharmacodynamically guided uptitration to 9 mg) or erdafitinib 8 mg plus intravenous cetrelimab 240 mg once every 2 weeks at cycles 1-4 and 480 mg once every 4 weeks thereafter. Primary end points were investigator-assessed confirmed overall response rate (ORR) and safety; secondary end points included duration of response (DOR), progression-free survival, and overall survival (OS). No statistical hypotheses were tested.
Results: At data cutoff, 87 patients were randomly assigned and treated (erdafitinib, n = 43; erdafitinib plus cetrelimab, n = 44). Of 64 patients with PD-L1 expression data, 56 (87.5%) had low levels of PD-L1 expression (combined positive score <10). Median survival follow-up was 14.2 months. Investigator-assessed confirmed ORR for erdafitinib was 44.2% (95% CI, 29.1 to 60.1) with one complete response (CR); median DOR and median OS were 9.7 months (95% CI, 4.6 to not estimable [NE]) and 16.2 months (95% CI, 8.3 to NE), respectively. Investigator-assessed confirmed ORR for erdafitinib plus cetrelimab was 54.5% (95% CI, 38.8 to 69.6), with six (13.6%) CRs; median DOR and median OS were 11.1 months (95% CI, 8.8 to NE) and 20.8 months (95% CI, 12.0 to NE), respectively. The most frequent treatment-related adverse events (TRAEs) were hyperphosphatemia (83.7% and 68.2% in erdafitinib and erdafitinib plus cetrelimab groups, respectively), stomatitis (69.8% and 56.8%), and dry mouth (37.2% and 56.8%). Grade ≥3 TRAEs occurred in 46.5% and 45.5% of patients receiving erdafitinib and erdafitinib plus cetrelimab, respectively.
Conclusion: First-line erdafitinib monotherapy and erdafitinib plus cetrelimab demonstrated antitumor activity and a manageable safety profile in cisplatin-ineligible patients with mUC.
Journal of Clinical Oncology , article en libre accès, 2026