DISCUS Trial Shows 3 Cycles of Chemotherapy Improve Quality of Life Without Compromising Efficacy in Advanced Urothelial Cancer
核心洞察
The phase 2 DISCUS trial demonstrated that 3 cycles of platinum-based chemotherapy (搜索) followed by avelumab maintenance significantly improved quality of life scores compared to 6 cycles in patients with advanced urothelial cancer (搜索).
Efficacy outcomes including overall survival, progression-free survival, and response rates were similar between the 3-cycle and 6-cycle treatment arms, with median overall survival of 18.9 months in both groups.
More patients completed the shorter 3-cycle regimen (78%) compared to the 6-cycle regimen (40%), potentially facilitating better access to maintenance immunotherapy.
The phase 2 DISCUS trial has demonstrated that reducing platinum-based chemotherapy (搜索) from 6 to 3 cycles before maintenance avelumab significantly improves quality of life without compromising treatment efficacy in patients with advanced urothelial cancer (搜索). The findings, presented at the 2025 European Society for Medical Oncology (搜索) Congress in Berlin, Germany, could reshape treatment approaches in this patient population.
Primary Quality of Life Endpoint Met
The study's primary endpoint was achieved, showing a clinically significant difference in quality of life outcomes between treatment arms. Patients receiving 3 cycles of chemotherapy experienced a mean change in The European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30) global health status score of 0.0 (95% CI, -5.0 to 5.2) compared with -8.5 (95% CI, -14.1 to -2.9) among those receiving 6 cycles.
The difference of 8.5 points (95% CI, 0.7-16.3; P = .016) significantly favored the 3-cycle arm, meeting the study's primary endpoint. "The most important highlight coming from the DISCUS trial is that we can explore the need for [fewer] cycles of combination [chemotherapy] in the era of antibody-drug conjugates in metastatic urothelial cancer (搜索)," said Enrique Grande, MD, director of the Department of Medical Oncology at Quirónsalud (搜索) in Madrid, Spain.
Treatment Completion and Efficacy Outcomes
The study enrolled 267 patients randomly assigned to receive either 3 or 6 cycles of platinum-based chemotherapy (搜索) followed by maintenance avelumab. Treatment completion rates differed substantially between arms, with 78% of patients completing all 3 cycles compared to only 40% completing all 6 cycles of allocated treatment.
Despite the reduced chemotherapy duration, efficacy outcomes remained comparable between groups. The overall response rate was 24% in the 3-cycle arm versus 27% in the 6-cycle arm. Among response-evaluable patients, complete response rates were identical at 13% in both arms, while partial response rates were 48% and 46% respectively.
Survival outcomes showed no significant differences between treatment arms. Median progression-free survival was 8.0 months (95% CI, 6.7 to 11.9) in the 3-cycle arm compared to 9.0 months (95% CI, 6.9 to 12.7) in the 6-cycle arm. Median overall survival was 18.9 months in both arms (HR, 1.15; 95% CI, 0.72 to 1.86; P = .56).
Safety Profile and Treatment Tolerability
The shorter chemotherapy regimen demonstrated improved tolerability. Grade 3 to 4 treatment-related adverse events occurred in 11.9% of patients in the 3-cycle arm compared to 15.7% in the 6-cycle arm. Grade 1/2 treatment-related adverse effects occurred at rates of 37% and 46% in the 3- and 6-cycle arms respectively.
Discontinuation of chemotherapy due to treatment-related adverse events was notably lower in the 3-cycle arm (2% vs 10%). The most common any-grade treatment-related adverse events in the overall population included anemia (9%), neutropenia (9%), nausea (8%), and fatigue (6%).
Study Design and Patient Population
DISCUS was an adaptive, open-label study enrolling patients with locally advanced or metastatic urothelial cancer (搜索) eligible for platinum-based chemotherapy (搜索). Patients were required to have no prior systemic therapy for metastatic disease, ECOG performance status of 0 to 2, and no contraindications for immunotherapy.
The median age in the study population was 71 years (range, 44-91), with 73% of patients aged 65 or older. Most patients were male (72%), did not have liver metastases (81%), had an ECOG performance status of 0 (73%), and received cisplatin plus gemcitabine (59%).
Clinical Implications
Grande noted that "more patients [who received] 3 cycles of platinum-based chemotherapy (搜索) went on to receive maintenance avelumab, which may facilitate long-term efficacy." The higher completion rate for the shorter regimen could improve access to maintenance immunotherapy, potentially benefiting long-term outcomes.
While the researchers cannot claim noninferiority in terms of overall survival due to the trial design, Grande emphasized that "OS is still evolving. We will need more data with longer follow-up." The findings suggest that reducing chemotherapy duration while maintaining efficacy could become an important consideration in treatment planning for advanced urothelial cancer (搜索).