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
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 patient-focused outcomes exploring shorter duration of therapy are feasible. (NCT06892860).
Source: Powles T, Hussain SA, Climent MA, et al. 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. Ann Oncol. Published online October 17, 2025. doi:10.1016/j.annonc.2025.10.011
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