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☆

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Abstract

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 three versus six cycles followed by avelumab. Patients and methods: This randomized phase II trial compared three versus six cycles (3C arm versus 6C arm) of chemotherapy followed by avelumab in patients receiving first-line treatment for mUC. This trial had co-primary endpoints of patient-reported outcomes (PROs), defined as change from baseline to cycle 6 on the global health status/QoL score, and superior overall survival (OS). Secondary endpoints included progression-free survival (PFS), overall response rate, and safety. Here, we report the final PRO analysis and interim OS. Results: A total of 267 patients were randomized (133 to 3C arm, 134 to 6C arm). Forty-two percent received gemcitabine/cisplatin and 58% gemcitabine/carboplatin. Seventy-eight percent and 40% of patients completed three and six cycles as allocated. Seventy-four percent of patients received avelumab in the 3C arm, versus 56% in the 6C arm. The mean QoL change between baseline and cycle 6 was 0 [95% confidence interval (CI) −5.9 to 5.2] in the 3C arm versus −8.5 (95% CI −14.1 to −2.9) in the 6C arm, 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 arm) versus 24% (6C arm) of patients. OS was not significant (18.9 months in both arms [hazard ratio (HR) 1.15, 95% CI 0.72-1.86, P = 0.56]. Median PFS was 8.0 months (95% CI 6.7-11.9 months) in the 3C arm versus 9.0 months (95% CI 6.9-12.7 months) in the 6C arm (HR 1.05, 95% CI 0.73-1.53). Median grade 3-4 treatment-related adverse events occurred in 11.9% (3C arm) versus 15.7% (6C arm). Conclusions: Three cycles of chemotherapy followed by maintenance avelumab is associated with better QoL than six cycles. Randomized trials with patient-focused outcomes exploring shorter duration of therapy are feasible (NCT06892860).