Top 5 GU Oncology Presentations From ESMO Congress 2025
Key Points
-
The PSMAddition trial found lutetium-177-prostate-specific membrane antigen-617 (177Lu-PSMA-617) improved treatment outcomes for patients with metastatic hormone-sensitive prostate cancer (mHSPC)
-
In CAPItello-281, capivasertib combined with standard of care significantly increased survival for patients with mHSPC with PTEN deficiency.
-
The final POTOMAC analysis reported the addition of durvalumab to standard induction and maintenance reduced the risk of relapse in high-risk, non-muscle-invasive bladder cancer (NMIBC).
-
For cisplatin-ineligible patients with muscle-invasive bladder cancer (MIBC), perioperative enfortumab vedotin (EV) plus pembrolizumab significantly improved survival and response rate, according to data from KEYNOTE-905.
-
In the IMvigor-11 trial, initiating adjuvant atezolizumab based on circulating tumor DNA (ctDNA) status increased survival rates for ctDNA-positive patients with MIBC.
ESMO Congress 2025 GU Cancer Updates
The cohosts of the Oncology Brothers podcast, Rahul Gosain, MD, MBA, of Wilmot Cancer Institute, and Rohit Gosain, MD, of Roswell Park Comprehensive Cancer Center, met with Stephanie Berg, DO, of Dana-Farber Cancer Institute, to discuss major presentations in genitourinary (GU) cancers presented at the European Society of Medical Oncology (ESMO) Congress 2025. The doctors discussed data from the PSMAddition, CAPItello-281, POTOMAC, KEYNOTE-905, and IMVigor011 trials.
PSMAddition: First Interim Efficacy Analysis
The phase 3 PSMAddition trial compared 177Lu-PSMA-617 plus androgen deprivation therapy (ADT) and androgen receptor pathway inhibitor (ARPI) against a control arm of ADT plus ARPI. The trial enrolled patients with treatment-naïve or minimally-treated PSMA-positive (PSMA+) mHSPC with one or more PSMA+ metastatic lesions. The ESMO Congress 2025 presentation covered the first interim efficacy analysis.
With a median follow-up of 23.6 months, the study met its primary endpoint, showing a significant improvement in radiographic progression-free survival (rPFS), and a positive overall survival (OS) trend.
The 177Lu-PSMA-617 arm (n = 572) had 139 (24.3%) rPFS events while the control arm (n = 572) had 172 (30.1%) events (hazard ratio [HR], 0.72; 95% CI, 0.58-0.90; P = .002). The median rPFS was not estimable (NE) for either the 177Lu-PSMA-617 arm (95% CI, NE-NE) or the control arm (95% CI, 29.73-NE).
Additionally, there were 85 (14.9%) OS events in the 177Lu-PSMA-617 arm versus 99 (17.3%) in the control arm (HR, 0.84; 95% CI, 0.63-1.13; P = .125). Median OS was NE for each arm (95% CI, NE-NE). The objective response rate was 85.3% (95% CI, 79.9-89.6) with 177Lu-PSMA-617 compared with 80.8% (95% CI, 74.8-85.8) in the control arm.
“This was really practice changing, and it will be interesting to see how this plays out with FDA approvals moving forward in this [mHSPC] space,” said Dr. Berg.
CAPItello-281: Capivasertib in PTEN-Deficient mHSPC
The phase 3 CAPItello-281 trial evaluated capivasertib or placebo combined with abiraterone plus prednisone/prednisolone and ADT in patients with mHSPC with PTEN deficiency. PTEN deficiency was defined as a lack of expression in at least 90% of viable malignant cells. The study randomized 1012 total patients between the capivasertib arm (n = 507) and the placebo arm (n = 505).
The median rPFS was 33.2 months (95% CI, 25.8-44.2) in the capivasertib arm versus 25.7 months (95% CI, 22.0-29.9) in the placebo arm (HR, 0.81; 95% CI, 0.66-0.98; P = .034). The median OS was not calculable (NC) for both the capivasertib arm (95% CI, 42.5-NC) and placebo arm (95% CI, NC-NC), though the data numerically favored capivasertib (HR, 0.90; 95% CI, 0.71-1.15; P = .401). Notably, the rPFS benefit of capivasertib increased in subgroups with higher PTEN deficiency cutoffs.
After reviewing PSMAddition and CAPItello-281, the doctors considered what maneuvering through all the available treatment options in the HSPC space will look like. Since patients with HSPC can live for years and receive several lines of therapy, thoughtful sequencing to achieve the highest benefit with the least toxicity is key, Dr. Berg said.
POTOMAC: Results From the Final Analysis
The ESMO Congress 2025 included the final analysis of the phase 3 POTOMAC trial, which observed durvalumab plus Bacillus Calmette-Guérin (D+BCG) in BCG-naïve, high-risk, NMIBC. POTOMAC randomized 1018 postsurgery patients with NMIBC to either D+BCG induction and maintenance (n = 339), D+BCG induction only (n = 339), or standard BCG induction and maintenance (n = 340).
Over a median follow-up of 60.7 months, the study met its primary disease-free survival (DFS) endpoint with a 32% decrease in risk of recurrence or death for D+BCG induction and maintenance versus BCG induction and maintenance (HR, 0.68; 95% CI, 0.50-0.93; P = .0154).
The D+BCG induction and maintenance arm had a 24-month DFS rate of 86.5% (95% CI, 82.2-89.8) compared with 81.6% (95% CI, 76.9-85.3) in the BCG induction and maintenance arm. D+BCG induction alone did not significantly improve DFS versus BCG induction and maintenance (HR, 1.14; 95% CI, 0.86-1.50). The addition of durvalumab did not impact OS compared with the standard of care (HR, 0.80; 95% CI, 0.53-1.20).
The POTOMAC data further support the potential of immunotherapy in the NMIBC space, and the doctors agreed that community oncologists may consider partnering more closely with urology colleagues when planning treatments for these patients.
KEYNOTE-905 ESMO Congress 2025 Update
The standard of care for cisplatin-ineligible patients with MIBC is radical cystectomy plus pelvic lymph node dissection. The phase 3 KEYNOTE-905 trial evaluated the addition of perioperative EV plus pembrolizumab to standard surgical treatment. The control arm received standard surgery without perioperative therapy.
After a median follow-up of 25.6 months (range, 11.8-53.7), 149 of 170 (87.6%) patients in the EV plus pembrolizumab arm and 156 of 174 (89.7%) in the control arm completed surgery.
Perioperative EV plus pembrolizumab significantly improved the primary endpoint of event-free survival (EFS) with median EFS NR in the study arm compared with 15.7 months in the control arm (HR, 0.40; 95% CI, 0.28-0.57; P < .001). Perioperative EV plus pembrolizumab also significantly improved OS (NR vs 41.7 months; HR, 0.50; 95% CI, 0.33-0.74; P < .001) and pathological complete response rate (57.1% vs 8.6%; 95% CI, 39.5-56.5; P < .001).
Dr. Rohit Gosain noted that it’s essential to manage side effects associated with EV, and oncologists should monitor for hyperglycemia, neuropathy, and severe skin toxicities when using this regimen.
IMVigor011: Data Presented at ESMO 2025
The phase 3 IMvigor011trial evaluated using ctDNA to guide initiation of adjuvant atezolizumab in patients with high-risk MIBC. The trial enrolled 761 patients in postcystectomy surveillance, of which 250 tested positive for ctDNA and were randomized to adjuvant atezolizumab (n = 167) or placebo (n = 83).
At a median follow-up of 16.1 months, the atezolizumab arm had significantly improved median DFS at 9.9 months (95% CI, 7.2-12.7) versus 4.8 months (95% CI, 4.1-8.3) in the placebo arm (HR, 0.64; 95% CI, 0.47-0.87; P = .0047). The atezolizumab and placebo arms had 12-month DFS rates of 44.7% and 29.6%, respectively.
Atezolizumab significantly improved median OS at 32.8 months (95% CI, 27.7-NE) versus 21.1 months (95% CI, 14.7-NE) with placebo (HR, 0.59; 95% CI, 0.39-0.90; P = .0131). The 12-month OS rates were 85.1% with atezolizumab and 70.0% with placebo. IMvigor011 also reported that patients who persistently tested negative for ctDNA had low rates of recurrence.