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A PEER-TO-PEER CLINICAL CONVERSATION
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| Complete Response in Low-Grade UTUC with Padeliporfin Therapy in the ENLIGHTED Trial |
| Vitaly Margulis, MD |
| Zachary Klaassen speaks with Vitaly Margulis about updates from the ENLIGHTED trial. This prospective phase III single-arm study targets low-grade upper tract urothelial cancer using padeliporfin, a photosensitizing chlorophyll derivative combined with light delivery. |
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Highlights from the 2025 American Society of Clinical Oncology Annual Meeting |
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State of the Science: Advancing Frontiers—Novel Diagnostics and Therapeutics in Renal Cell Carcinoma and Urothelial Carcinoma
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| Functional Imaging in Renal Cell Carcinoma: Enhancing Diagnosis and Treatment Strategies
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| Michael Hofman, MBBS, FRACP, FAANMS, FICIS, GAICD
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| Michael Hofman highlighted the growing role of functional imaging and theranostics in renal cell carcinoma (RCC), particularly targeting carbonic anhydrase IX (CA-IX) in clear cell RCC. New PET/CT imaging agents like ⁶⁸Ga-DPI-4452 and ⁸⁹Zr-girentuximab show high diagnostic accuracy, while theranostic applications using ¹⁷⁷Lu-labeled agents are under investigation, despite some toxicity concerns. The field is rapidly advancing, with promising implications for diagnosis, treatment, and patient selection. |
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| Antibody-Drug Conjugates in Urothelial Carcinoma: Bridging Innovation and Community Practice |
| Elizabeth Marie Wulff-Burchfield, MD |
| Elizabeth Wulff-Burchfield highlighted the growing role of ADCs like enfortumab vedotin and trastuzumab deruxtecan in treating advanced urothelial carcinoma, demonstrating significant survival benefits in clinical trials. She emphasized the challenges community oncologists face—limited access to molecular testing, financial burdens, and infrastructure gaps—and called for strategies such as role realignment, guideline-driven adoption, and expanded education to ensure broader access to these innovations in non-academic settings. |
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Rapid Oral Abstract Session: Genitourinary Cancer—Kidney and Bladder
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| Five-Year Follow-up Results from the Phase 3 KEYNOTE-564 Study of Adjuvant Pembrolizumab for the Treatment of Clear Cell RCC |
| Naomi Haas, MD |
| Naomi Haas presented five-year follow-up results from the phase 3 KEYNOTE-564 study, confirming that adjuvant pembrolizumab significantly improves both disease-free and overall survival in patients with clear cell RCC at high risk of recurrence. With a 5-year disease-free survival rate of 60.9% versus 52.2% and overall survival of 87.7% versus 82.3% compared to placebo, the benefits were consistent across all subgroups. |
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| Zanzalintinib + Nivolumab ± Relatlimab in Patients with Previously Untreated Clear Cell RCC: Results from an Expansion Cohort of the Phase 1b STELLAR-002 Study |
| Jad Chahoud, MD |
| Jad Chahoud presented data from the STELLAR-002 phase 1b study showing that zanzalintinib combined with nivolumab—with or without relatlimab—demonstrated acceptable tolerability and encouraging antitumor activity in treatment-naïve clear cell RCC patients. The zanzalintinib + nivolumab arm achieved a 63% objective response rate and 90% disease control rate, while the triple combo arm showed a 33% response rate. Adverse events were manageable, with low rates of severe palmar-plantar erythrodysesthesia and no grade 5 events. |
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| Ipilimumab and Nivolumab in Patients with Metastatic Clear Cell RCC Treated on the Phase 3 PDIGREE (Alliance A031704) Trial: Results from Step 1 Analysis |
| Tian Zhang, MD |
| Tian Zhang presented Step 1 results from the phase 3 PDIGREE trial evaluating ipilimumab + nivolumab as first-line therapy for metastatic clear cell RCC. Among 1,111 enrolled patients, one-third discontinued early—mostly due to adverse events—while 67% continued to Step 2, with only 1.2% achieving complete response at 12 weeks. The data highlight real-world tolerability and early outcomes of this regimen in a diverse, U.S.-based population, informing future sequencing strategies. |
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| AREN1721, a Randomized Phase 2 Trial of Axitinib + Nivolumab Combination Therapy Versus Single Agent Nivolumab for the Treatment of TFE/translocation RCC Across All Age Groups: An NCI NCTN Phase 2 Study |
| James I. Geller, MD |
| James Geller presented results from the phase 2 AREN1721 trial, which evaluated axitinib + nivolumab versus nivolumab alone in patients with translocation RCC, a rare and aggressive RCC subtype. Despite early closure due to poor accrual (13 eligible patients), the combination therapy significantly improved progression-free survival (10.5 vs. 1.8 months; p = 0.0004) and showed partial responses in 33% of patients, while nivolumab alone had no responses. |
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| ENLIGHTED Phase 3 Study: Interim Results of Efficacy and Safety of Padeliporfin VTP Therapy in the Treatment of Low-Grade Upper Tract Urothelial Cancer
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| Vitaly Margulis, MD
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| Vitaly Margulis presented interim results from the ENLIGHTED phase 3 trial evaluating padeliporfin vascular targeted photodynamic (VTP) therapy for low-grade upper tract urothelial cancer. Among 37 evaluable patients, the therapy showed an 86.5% overall response rate and 73% complete response, with mostly mild, short-lived side effects, supporting its potential as an effective and organ-sparing treatment. Recruitment is ongoing, and final results are expected to support regulatory approval.
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| Sasanlimab in Combination with BCG in BCG-Naive High-Risk NMIBC: Event-Free Survival Subgroup Analyses Based on Disease Stage from the CREST Study |
| Thomas Powles, MD |
| Thomas Powles presents subgroup analyses from the phase 3 CREST study evaluating sasanlimab plus BCG in BCG-naive, high-risk non–muscle-invasive bladder cancer. These post hoc results showed that combining sasanlimab with BCG significantly improved 3-year event-free survival in patients with either CIS or T1 disease compared to BCG alone. |
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| CLONEVO: Preoperative Abemaciclib for Cisplatin Ineligible MIBC with Molecular Response Assessment
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| Bishoy Faltas, MD
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| Bishoy Faltas presents the CLONEVO trial, the first window-of-opportunity study assessing preoperative abemaciclib in cisplatin-ineligible patients with muscle invasive bladder cancer. The trial demonstrated that short-term abemaciclib was well tolerated and led to pathologic complete response or downstaging in nearly half of evaluable patients. Molecular analyses confirmed on-target activity and revealed suppression of E2F-driven proliferation and DNA repair pathways, supporting future combinations with agents like enfortumab vedotin.
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| First Results of SURE-02: A Phase 2 Study of Neoadjuvant Sacituzumab Govitecan + Pembrolizumab, Followed by Response-Adapted Bladder Sparing and Adjuvant Pembrolizumab, in Patients with MIBC |
| Andrea Necchi, MD |
| Andrea Necchi presents interim results from the SURE-02 phase 2 trial evaluating neoadjuvant sacituzumab govitecan plus pembrolizumab, followed by response-adapted bladder-sparing strategies and adjuvant pembrolizumab in MIBC patients who were ineligible for or refused chemotherapy. The combination demonstrated a promising clinical complete response rate of 38.7%, allowing approximately 40% of patients to avoid radical cystectomy through re-TURBT. |
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| 9MW2821, a Novel Nectin-4 Antibody Drug Conjugate, Combined with Toripalimab in Treatment-Naïve Patients with Locally Advanced or Metastatic Urothelial Carcinoma: Results from a Phase 1b/2 Study |
| Xinan Sheng, MD |
| Xinan Sheng presents results from a phase 1b/2 study evaluating the combination of 9MW2821, a novel nectin-4 antibody-drug conjugate, with toripalimab in treatment-naïve patients with locally advanced or metastatic urothelial carcinoma. The combination demonstrated a high objective response rate of 87.5%, with manageable safety and no new safety signals. |
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Poster Session: Genitourinary Cancer—Kidney and Bladder
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| Real-World Quality of Life for Patients with Metastatic RCC Treated with Systemic Therapy in the Prospective Observational ODYSSEY Study |
| Benjamin Maughan, MD, PharmD |
| Benjamin Maughan presented results from the ODYSSEY study, a prospective observational analysis of real-world quality of life in patients with metastatic RCC treated with systemic therapy. The study found that patients receiving IO-IO or IO-TKI regimens had worse baseline quality of life compared to those in clinical trials, with about one-third discontinuing or dying within 6 months. These findings highlight the challenges of translating trial-based outcomes into real-world settings and underscore the need for more patient-centered treatment approaches. |
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| ctDNA Monitoring in Patients with Advanced Urothelial Carcinoma Treated with Enfortumab Vedotin +/- Pembrolizumab |
| Kevin R Reyes, MD
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| Kevin Reyes presented a retrospective analysis showing that in patients with advanced urothelial carcinoma treated with enfortumab vedotin ± pembrolizumab, 79% experienced a ctDNA decrease and 33% achieved ctDNA clearance. Achieving ctDNA negativity within 2 months was associated with significantly improved progression-free survival, while failure to show a ctDNA decline predicted worse survival outcomes—highlighting the potential of ctDNA as an early treatment response biomarker.
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| Real-World Enfortumab Vedotin +/- Pembrolizumab–based Treatment Toxicity, Treatment Discontinuation, and Associations with Survival in Advanced Urothelial Carcinoma |
| Martin Kurian, MD |
| Martin Kurian presented real-world data on enfortumab vedotin ± pembrolizumab in advanced urothelial carcinoma, showing that while toxicities like skin reactions (60%) and neuropathy (47%) were common, treatment discontinuation was relatively infrequent. Interestingly, patients who developed certain toxicities had significantly longer overall survival, suggesting a potential association between treatment-related adverse events and improved outcomes. |
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| FGFR3 Alteration Status and Outcomes with Immune Checkpoint Inhibitors in Patients with Metastatic Urothelial Carcinoma |
| Shilpa Gupta, MD |
| Shilpa Gupta presented data showing that FGFR3 alterations alone do not predict outcomes to immune checkpoint inhibitors (ICIs) in metastatic urothelial carcinoma. However, patients with both FGFR3 alterations and high tumor mutational burden (≥10 mutations/Mb) showed a trend toward improved survival with ICIs, suggesting this combined biomarker may better predict benefit. These findings support further investigation in larger cohorts to validate FGFR3/TMB co-status as a potential predictive marker. |
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| Impact of Tumor Burden or Focality in Recurrent Low-Grade Intermediate-Risk Non-Muscle Invasive Bladder Cancer on Response to Treatment with UGN-102: A Substudy of the Phase 3 ENVISION Trial |
| John Sfakianos, MD |
| John Sfakianos presented a substudy of the phase 3 ENVISION trial evaluating whether tumor size or multifocality impacted response to UGN-102 in recurrent low-grade intermediate-risk non–muscle invasive bladder cancer. Complete response rates and durability of response at 12 months were favorable across all subgroups, with no statistically significant differences based on tumor burden or focality. These findings support UGN-102 as a promising treatment option regardless of baseline tumor characteristics. |
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| Duration of Response Following Treatment with UGN-102 in Patients with Recurrent, Low-Grade, Intermediate-Risk, Non-Muscle Invasive Bladder Cancer: 18-Month Data from the Phase 3 ENVISION Trial |
| Sandip M. Prasad, MD, MPhil |
| Sandip Prasad presented 18-month follow-up data from the phase 3 ENVISION trial, showing that UGN-102 led to a 79.6% complete response rate at 3 months in patients with recurrent low-grade, intermediate-risk non–muscle invasive bladder cancer. Among those who achieved a complete response, 80.6% remained disease-free at 18 months, confirming UGN-102 as a durable and promising non-surgical treatment option in this setting. |
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