Three versus six cycles of platinum-based chemotherapy followed by avelumab maintenance as first-line treatment for advanced urothelial cancer: the phase II DISCUS trial
Mené sur 267 patients atteints d'un cancer urothélial de stade avancé, cet essai randomisé de phase II détermine la durée optimale d'une chimiothérapie de première ligne à base de sels de platine (3 ou 6 cycles) puis évalue l'intérêt, du point de vue de la qualité de vie, de cette chimiothérapie suivie de l'avélumab en traitement d'entretien
Background: Six cycles of platinum-based chemotherapy followed by avelumab continues to be used in some circumstances in advanced/metastatic urothelial cancer (mUC). To investigate whether shorter chemotherapy duration improves quality of life (QoL) without worsening efficacy, this study compared 3 vs 6 cycles followed by avelumab.
Methods: This randomized phase II trial compared 3 vs 6 cycles (3C arm vs 6C arm) of chemotherapy followed by avelumab in patients receiving 1st line treatment for mUC. This trial had co-primary endpoints of patient-reported outcomes (PROs) defined as change from baseline to cycle6 on the Global Health Status QoL Score, and superior overall survival (OS). Secondary endpoints included progression-free survival (PFS), overall response rate (ORR), and safety. Here we report the final PRO analysis and interim OS.
Results: 267 patients were randomised (133 to 3C, 134 to 6C). 42% received gemcitabine/cisplatin and 58% gemcitabine/carboplatin. 78% and 40% of patients completed 3 and 6 cycles as allocated. 74% of patients received avelumab in 3C arm, vs 56% in 6C arm. The mean QoL change between baseline and cycle6 was 0 (95%CI: -5.9, 5.2) in 3C vs -8.5 (95%CI: -14.1, -2.9) in 6C, with a significant difference favouring 3C (+8.5 points, 95%CI: 0.7,16.3; p=0.016). Improvement in PRO scores was observed in 41% (3C) vs 24% (6C) of pts. OS was not significant (18.9 months in both arms (HR=1.15, 95% CI: 0.72,1.86; p=0.56)). Median PFS was 8.0 months (95% CI: 6.7,11.9) in 3C vs 9.0 months (95% CI: 6.9, 12.7) in 6C, HR=1.05 (95% CI: 0.73,1.53). Median Grade 3–4 TRAEs occurred in 11.9% (3C) vs 15.7% (6C).
Conclusion: 3 cycles of chemotherapy followed by maintenance avelumab is associated with better QoL than 6 cycles. Randomized trials with patients focused outcomes exploring shorter duration of therapy are feasible. (NCT06892860).
Annals of Oncology , résumé, 2025