DISCUS Trial: Shorter Chemo Regimen Improves QOL in Advanced Urothelial Cancer

Results from the phase 2 DISCUS trial (NCT06892860)¹ find that shorter periods of systemic therapy are feasible in patients with advanced or metastatic urothelial cancer, showing improved quality of life (QOL) and meeting the study’s primary end point.

The findings from the trial were announced at the 2025 European Society for Medical Oncology (ESMO) Congress on October 17, 2025 in Berlin, Germany, by Enrique Grande, MD, PhD, director of the Medical Oncology Program and Clinical Research lead at the MD Anderson Cancer Center in Madrid, Spain.²

The total number of patients was 267, with 133 patients in the 3-cycle arm and 134 patients in the 6-cycle arm. The median age of patients was 71 years (range, 44–91). Of the total patients, 19% (n = 50) had present liver metastasis. Patients were randomized 1:1 to receive either 6 cycles of gemcitabine plus cisplatin/carboplatin with maintenance treatment of avelumab (Bavencio) for up to 2 years, or 3 cycles of gemcitabine plus cisplatin/carboplatin with maintenance treatment of avelumab for up to 2 years.

The mean change in QOL with therapy for patients in the 3-cycle arm vs the 6-cycle arm was 0.0 (95% CI, -5.9–5.2) vs -8.5 (95% CI, -14.1– -2.9).

In the 6-cycle arm, approximately 20% of patients had improved QOL compared with approximately 40% of patients in the 3-cycle arm. Approximately 50% of patients in the 6-cycle arm saw worsened QOL vs approximately 40% of patients in the 3-cycle arm.

The difference in time to deterioration in global health status (GHS)/QOL between the 3-cycle and 6-cycle arm had a recorded hazard ratio (HR) of 0.81 (95% CI, 0.46–1.43) over the course of 12 months.

In patients in the 6-cycle arm, median overall survival (OS) was 18.86 months vs 18.92 months in patients in the 3-cycle arm (HR, 1.15; 95% CI, 0.72–1.86; P =.56).

Median progression-free survival (PFS) was 9 months in patients in the 6-cycle arm vs 8 months in patients in the 3-cycle arm (HR, 1.053; 95% CI, 0.725–1.527; P =.788).

Complete response was reported in 13% (n = 25) of the total number of patients, with 13% in both arms. Partial response was reported in 47% (n = 92), with 46% in the 6-cycle arm and 48% in the 3-cycle arm. Stable disease was reported in 31% (n = 61) of patients, with 30% in the 6-cycle arm and 33% in the 3-cycle arm.

Treatment-related adverse events (AEs) grades 1–4 occurred in 43% of patients in the 3-cycle arm, with the most common being nausea (4%), fatigue (3%), and asthenia (3%), all grade 1 or 2. In the 6-cycle arm, 57% of patients experienced AEs, with the most common being anemia (grade 1 or 2, 4%), neutropenia (grade 3 or 4, 4%), and nausea (grade 1 or 2, 4%).

Serious AEs occurred in 35% of patients in the 3-cycle arm vs 37% of patients in the 6-cycle arm, and grade 5 AEs occurred in 2% of patients in the 3-cycle arm and 0% in the 6-cycle arm. Platinum-based chemotherapy (PBC) discontinuation due to AEs occurred in 2% of patients in the 3-cycle arm and 10% of patients in the 6-cycle arm.

Background of the DISCUS trial

The DISCUS trial was designed to evaluate if 3 vs 6 cycles of PBC before maintenance avelumab could improve QOL using novel patient-focused end points. Enfortumab vedotin (Padcev) plus pembrolizumab (Keytruda) has become the new standard first-line treatment in advanced or metastatic urothelial cancer. Longer PBC exposure was thought to improve overall response rate (ORR), PFS, and OS; however, Grande noted during the presentation that “this has never been proven in prospective trials.” It was determined that maintenance avelumab significantly prolongs survival in patients with benefit from induction PBC.

Study Design of DISCUS

Patients received 1000 mg of gemcitabine every 3 weeks, AUC 4.5 or 5 of carboplatin, 70 mg of cisplatin, and 800 mg of maintenance avelumab every 2 weeks.

The primary end points of the trial were difference in GHS/QOL score between baseline and cycle 6 and OS. The secondary end points of the trial were safety and efficacy, including PFS and ORR.

Patient inclusion criteria included having locally advanced or metastatic urothelial cancer, being eligible for any PBC, being naive to prior systemic treatment for metastatic setting, having an ECOG score of 0 or 2, and not having contraindications for IO.

“DISCUS highlights the feasibility of exploring shorter periods of systemic therapy in [metastatic urothelial cancer], which is relevant in the era of [antibody-drug conjugate] therapy in [metastatic urothelial cancer] and beyond,” Grande concluded.

DECLARATIONS: Enrique Grande declared an advisory role or funding of continuous medical education with AbbVie, Adium, Advanced Accelerator Applications, Astellas, Astra Zeneca, AVEO, Bayer, Bristol Myers Squibb, Clovis-Oncology, Dr. Reddy’s, Eisai, Esteve, Eusa Pharma, GSK, IMVAX, IPSEN, ITM-Radiopharma, Janssen, Lilly, Merck KGaA, MSD, Novartis, Palex, Pfizer, Raffo, Roche, Rovi, Tecnofarma.

REFERENCES

1.Comparing 3 vs 6 cycles of platinum-based chemotherapy prior to maintenance avelumab in advanced urothelial cancer (DISCUS). ClinicalTrials.gov. Updated March 25, 2025. Accessed November 5, 2025. https://clinicaltrials.gov/study/NCT06892860

2.Grande E, Hussain S, Climent M, et al. DISCUS: A phase II study comparing 3 vs 6 cycles of platinum-based chemotherapy prior to maintenance avelumab in advanced urothelial cancer. Presented at: 2025 ESMO Congress; October 17-25, 2025; Berlin, Germany. Abstract LBA109.