DISCUS trial shows improved PROs with de-escalation of chemotherapy in mUC

Patients with locally advanced or metastatic urothelial carcinoma (la/mUC) who received shorter periods of platinum-based chemotherapy prior to maintenance avelumab (Bavencio) showed improved patient-reported outcomes with no detriment to overall survival (OS), according to initial data from the phase 2 DISCUS trial (NCT06892860).¹

The findings were presented by Enrique Grande, MD, at the 2025 European Society for Medical Oncology Congress in Berlin, Germany.

“Historically, we have been squeezing out chemotherapy in our patients, looking for more responses, deep responses, [and] long-term responses, believing that that would be translated into longer progression-free survival and overall survival. However, this has never been proved prospectively,” Grande explained.

Thus, the DISCUS trial was initiated to assess the feasibility of 3 vs 6 cycles of platinum-based chemotherapy prior to maintenance avelumab in this patient population. Patients enrolled in the trial needed to have la/mUC, an ECOG performance status of 0 to 2, and no contraindications for immunotherapy. Further, patients needed to be eligible for platinum-based chemotherapy and naïve to prior systemic treatment delivered in the metastatic setting.

Those enrolled in the trial (n = 267) were randomly assigned 1:1 to receive 6 cycles (n = 134) vs 3 cycles (n = 133) of gemcitabine plus cisplatin/carboplatin followed by maintenance avelumab for up to 2 years. The primary end point was the change from baseline to completion of cycle 6 in EORTC QLQ-C30 global health score/quality of life (GHS/QoL) scale score, as well as OS.

Overall, the trial met its primary end point, showing a mean change in GHS/QoL EORTC QLQ-C30 scores of 0.0 (95% CI, -5.9 to 5.2) in the 3 cycles arm vs -8.5 (95% CI, -14.1 to -2.9) in the 6 cycles arm (difference, 8.5; 95% CI, 0.7 to 16.3; P = .016).

Grande added, “We observed that more patients, numerically speaking, in the 3 cycles arm [had] improved quality of life vs those patients who were randomized to the 6 cycles arm, and more patients in the 6 cycles arm unfortunately got worse in terms of quality-of-life vs the 3 cycles arm.”

The time to deterioration in GHS/QoL was not found to be statistically significant between the 2 arms, with a hazard ratio of 0.81 (95% CI, 0.46 to 1.43).

In terms of efficacy, 6 cycles of platinum-based chemotherapy was not found to be superior to 3 cycles, with a median OS of 18.86 months (95% CI, 13.93 to NR) in the 6 cycles arm vs 18.92 months (95% CI, 12.81 to NR) in the 3 cycles arm (HR, 1.15; 95% CI, 0.72 to 1.86; P = .56). The investigators could not claim non-inferiority due to design limitations in the study. OS analysis remains ongoing.

“This is the new benchmark in terms of median survival that we can expect in the era of avelumab maintenance after induction platinum-based chemotherapy,” Grande noted.

Progression-free survival (PFS) was also comparable between arms, with a median PFS of 9.0 months (95% CI, 6.87 to 12.71) in patients who received 6 cycles of chemotherapy vs 8.0 months (95% CI, 6.70 to 11.89) in patients who received 3 cycles of chemotherapy (HR, 1.053; 95% CI, 0.725 to 1.527; P = .788).

There were numerically similar response rates seen in both arms, with responses reported in 49% of patients in the 6 cycles arm vs 61% in the 3 cycles arm. Notably, progressive disease as a best response was reported in 10% of patients in the 6 cycles arm and 6% of patients in the 3 cycles arm.

The investigators then sought to assess whether there was any particular subgroup that may benefit more or less from receiving 3 vs 6 cycles of chemotherapy in terms of quality-of-life.

Grande explained, “There is a consistent trend to benefit in terms of quality-of-life for those patients who reduced the number of cycles of platinum-based chemotherapy, particularly those patients who were treated with cisplatin chemotherapy and also with the presence of liver metastasis. This is just hypothesis generating.”

However, the investigators demonstrated no difference in OS nor PFS depending on the chemotherapy regimen received.

In terms of safety, grade 3/4 treatment-related adverse events (TRAEs) were reported in 11% of patients in the 6 cycles arm vs 6% of patients in the 3 cycles arm. Notably, 10% of patients in the 6 cycles arm discontinued treatment due to TRAEs, compared with 2% of patients in the 3 cycles arm.

“More patients in the 3 cycles arm of platinum-based chemotherapy went on to maintenance avelumab, which may facilitate long-term efficacy,” Grande concluded during the presentation. “I think the data are beyond the era of avelumab; now we are treating our patients with antibody drug conjugates. The most important highlight coming from the DISCUS trial is that we can do [a] de-escalation trial exploring the need for less cycles of combinations that we have in the era of antibody drug conjugates in metastatic urothelial cancer.”

REFERENCE

1. Grande E, Hussain SA, Duran MAC, 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 European Society for Medical Oncology Congress. October 17-21, 2025. Berlin, Germany. LBA109