Padcev (enfortumab vedotin-ejfv) / Astellas, Pfizer - LARVOL DELTA

Molecular pathology of bladder cancer. (PubMed, Histopathology) - "Alterations in FGFR3, commonly found in the luminal-papillary molecular subtype associated with low response to immunotherapy, are the target of erdafitinib. Enfortumab vedotin, which targets Nectin-4 (expressed in >95% of urothelial carcinomas), is approved for patients who progress after chemotherapy and/or immunotherapy...Sacituzumab govitecan, an antibody-drug conjugate directed against Trop-2, is effective in basal, luminal and stroma-rich subtypes but not in neuroendocrine carcinomas. In addition, therapies developed for HER2-positive breast cancer have shown efficacy in urothelial carcinoma, with recent data from the DESTINY pan-tumour phase II trial leading to FDA approval of trastuzumab deruxtecan for HER2-overexpressing metastatic urothelial carcinoma. This paper is a comprehensive review of the molecular pathology of bladder cancer, highlighting advances in molecular classification, biomarkers and personalized therapies. The transition from morphology-based..."

Biomarker • IO biomarker • Journal • Review • Bladder Cancer • Breast Cancer • Endocrine Cancer • Genito-urinary Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Neuroendocrine Carcinoma • Oncology • Solid Tumor • Urothelial Cancer • FGFR3 • HER-2 • KDM6A • KMT2D • PIK3CA • RB1 • TP53

Immunotherapy for urological cancers in 2025 (PubMed, Magy Onkol) - "By 2025, immunotherapy has become the therapeutic basis for UC and RCC, both in metastatic and curative treatments. In PCa and TGCT, immunotherapy options remain in the experimental phase, but research is ongoing with new combinations and biomarker-driven strategies."

IO biomarker • Journal • Review • Genito-urinary Cancer • Germ Cell Tumors • Microsatellite Instability • Oncology • Prostate Cancer • Renal Cell Carcinoma • Solid Tumor • Testicular Cancer • Urethral Cancer • Urothelial Cancer • MSI

Invited Discussant – Asian perspectives on: 1- Perioperative (periop) enfortumab vedotin (EV) plus pembrolizumab (pembro) in participants (pts) with muscle-invasive bladder cancer (MIBC) who are cisplatin-ineligible: The phase III KEYNOTE-905 study & 2 - IMvigor011: A phase III trial of circulating tumour (ct)DNA-guided adjuvant atezolizumab vs placebo in muscle-invasive bladder cancer (ESMO Asia 2025) - No abstract available

Circulating tumor DNA • Clinical • P3 data • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

Perioperative (periop) enfortumab vedotin (EV) plus pembrolizumab (pembro) in participants (pts) with muscle-invasive bladder cancer (MIBC) who are cisplatin-ineligible: The phase III KEYNOTE-905 study (ESMO Asia 2025) - No abstract available

Clinical • P3 data • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

A patient with metastatic upper tract urothelial carcinoma with EGFR exon 20 insertion and MTAP loss responding to amivantamab and pemetrexed-based chemotherapy (ESMO Asia 2025) - P2 | "Gemcitabine and carboplatin were started but lung metastasis worsened. He was switched to pembrolizumab without significant response. He was then given sacituzumab govitecan, with initial improvement but progressed later. He later had enfortumab vedotin and rechallenged carboplatin with nab-paclitaxel, and had further enlargement of lung metastasis...Our case offers insights into a patient with refractory urothelial carcinoma with EGFR exon 20 insertion and MTAP loss, having early and durable response to amivantimab and pemetrexed-carboplatin despite the failure of multiple prior therapies. This supports further investigation of broad molecular profiling and biomarker-guided trials in urothelial carcinoma to understand tissue-specific effects of genetic alterations."

Clinical • EGFR exon 20 • IO biomarker • Metastases • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Urothelial Cancer • CDKN2A • CDKN2B • EGFR • FGFR • HER-2 • MTAP • PD-L1 • PIK3CA • TP53

Patient-reported outcome measures for toxicities and HRQoL in cancer patients treated with antibody-drug conjugates: A systematic review (ESMO Asia 2025) - "Unique toxicities were reported, such as keratopathy with belantamab mafodotin, for which OSDI was used in the DREAMM-2 study, and dysgeusia with enfortumab vedotin, assessed using CiTAS in one observational study...In the DESTINY-Breast series, trastuzumab deruxtecan was associated with interstitial lung disease, yet no PROM is currently available to monitor this toxicity. Current PROMs are not tailored to the unique toxicity profiles of ADCs. Current PROMs are not tailored to the unique toxicity profiles of ADCs. There is an urgent need to develop and validate tools that capture symptoms such as ocular toxicity, pulmonary toxicity, and dysgeusia. Integrating these instruments into clinical trials and routine care will improve toxicity monitoring and enable more accurate, patient-centered quality-of-life assessments."

Clinical • Patient reported outcomes • Review • Brain Cancer • Breast Cancer • Glioblastoma • Hematological Malignancies • Lymphoma • Multiple Myeloma • Oncology • Ovarian Cancer • Solid Tumor • Urothelial Cancer

Impact of steroid premedication on the efficacy and cutaneous toxicity of enfortumab vedotin in advanced urothelial carcinoma (ESMO Asia 2025) - "Steroid premedication had no significant impact on the clinical efficacy of EV. While the incidence and severity of EV-related cutaneous toxicity appeared lower with premedication, the differences were not statistically significant."

Clinical • Metastases • Oncology • Solid Tumor • Urothelial Cancer

JAVEMACS chart review study of avelumab maintenance therapy for advanced urothelial carcinoma (aUC) in Japan: Subgroup analyses based on eligibility for cisplatin or platinum-based chemotherapy (PBC) (ESMO Asia 2025) - "Of pts who discontinued avelumab in the CE, CI/PE, and PI subgroups, second- line therapy was received by 60/84 (71%), 106/150 (71%), and 15/24 (63%), including enfortumab vedotin in 36/60 (60%), 72/106 (68%), and 12/15 (80%), respectively. Data from the real-world JAVEMACS study show the effectiveness of avelumab maintenance in pts with aUC not progressed after 1L PBC, including pts considered ineligible for cisplatin or PBC per standard criteria."

Clinical • Metastases • Review • Oncology • Solid Tumor • Urothelial Cancer

Real-world outcomes of enfortumab vedotin plus pembrolizumab in advanced urothelial carcinoma: First multicenter results from Taiwan (ESMO Asia 2025) - "In this LA/mUC cohort treated with EVP, the efficacy aligns with clinical trial, with a notable association between CR and prolonged DoT. A substantial proportion of pts who discontinued tx after achieving response, then PD, reinforcing the importance of continuing tx to sustain clinical benefit."

Clinical • Metastases • Real-world • Real-world evidence • Oncology • Solid Tumor • Urothelial Cancer

A retrospective comparison of outcomes of enfortumab vedotin in previously treated metastatic urothelial carcinoma: Pure versus variant histology (ESMO Asia 2025) - "Our study found no statistically significant differences in ORR, PFS, or OS when comparing pure UC to its histological variants. Due to the limitations of its retrospective design and sample size, these findings underscore the need for further investigation. Prospective randomized study is warranted for a comprehensive evaluation of EV outcomes in mUC with histological variants."

Metastases • Retrospective data • Oncology • Solid Tumor • Urothelial Cancer

Enfortumab vedotin outcomes in metastatic upper tract urothelial carcinoma: A comparison of ureteral and renal pelvic primaries after prior systemic therapy – A single center retrospective study (ESMO Asia 2025) - "Our study revealed that while EV demonstrated comparable ORR between metastatic UC originating from the ureter and the renal pelvis, OS was significantly worse in patients with ureteral origin tumors. This suggests a more aggressive underlying disease biology, highlighting the need for further research into individualized therapeutic strategies for this distinct patient population."

Metastases • Retrospective data • Oncology • Solid Tumor • Urothelial Cancer

JAVEMACS chart review study of avelumab maintenance therapy for advanced urothelial carcinoma (aUC) in Japan: Subgroup analyses based on histological subtype (ESMO Asia 2025) - "Of pts who discontinued avelumab in the pure UC and variant subgroups, second-line therapy was received by 155/226 (69%) and 30/38 (79%), including enfortumab vedotin in 99/155 (64%) and 21/30 (70%), respectively. Real-world data from Japan show the effectiveness of avelumab maintenance in pts with aUC not progressed after 1L PBC, including pts with pure UC or histological subtypes."

Clinical • Metastases • Review • Oncology • Solid Tumor • Urothelial Cancer

JAVEMACS chart review study of avelumab maintenance for advanced urothelial carcinoma (aUC): Analyses by primary tumour location (ESMO Asia 2025) - "In the UTUC and BC subgroups, respectively, creatinine clearance ≥60 mL/min was 20% and 42%, while 50% and 62% of patients received gemcitabine + cisplatin, 41% and 26% received gemcitabine + carboplatin as 1L PBC. Among those who discontinued avelumab, 75% (100/133) of UTUC and 67% (98/147) of BC patients received second-line therapy, with 72% (72/100) and 60% (59/98) receiving enfortumab vedotin (EV), respectively... The subgroup analysis of the JAVEMACS study revealed that in patients treated with avelumab 1L maintenance therapy, similar improvements in survival outcomes were observed in both UTUC and BC subgroups. Additionally, in the Japanese real world, EV was frequently used as 2L therapy, regardless of primary tumor location. These results help inform clinical decision-making for optimal patient management, as prognosis may vary by tumour location."

Clinical • Metastases • Review • Bladder Cancer • Oncology • Solid Tumor • Urothelial Cancer

Reply to Jorge Esteban-Villarrubia and Guillermo De Velasco's Letter to the Editor re: Daniel S. Roberson, Vidit Sharma, Stephen A. Boorjian, et al. Consolidative Surgery for Advanced Urothelial Carcinoma Following Induction Enfortumab Vedotin and/or Immune Checkpoint Inhibitor Therapy: A Multicenter Analysis. Eur Urol 2025;88:212-4. (PubMed, Eur Urol) - No abstract available

Checkpoint inhibition • Journal • Oncology • Solid Tumor • Urothelial Cancer

A phase II open-label study of enfortumab vedotin in patients with previously treated locally advanced, recurrent, or metastatic pancreatic adenocarcinoma (EPIC). (ASCO-GI 2026) - P2 | "Funded by Astellas Clinical Trial Registration Number: NCT05915351 The full, final text of this abstract will be available on Jan 05 at 05:00 PM EST."

Clinical • Metastases • P2 data • Gastrointestinal Cancer • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer

A phase II study of enfortumab vedotin in patients with advanced or metastatic colorectal cancer or hepatocellular carcinoma. (ASCO-GI 2026) - P2 | "Funded by Funding and enfortumab vedotin drug support provided from Astellas Pharma Global Development, Inc./Pfizer, Inc. through the Investigator Sponsored Research program Clinical Trial Registration Number: NCT06553885 The full, final text of this abstract will be available on Jan 05 at 05:00 PM EST."

Clinical • Metastases • P2 data • Colorectal Cancer • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor

Risk Signals of Antibody-Drug Conjugates in Bladder Cancer: A Real-World FAERS Study. (PubMed, Clin Epidemiol) - "Disproportionality analyses, including the reporting odds ratio (ROR), proportional reporting ratio (PRR), and Bayesian confidence propagation neural network (BCPNN), were used to detect significant adverse drug event (ADE) signals for four ADCs in bladder cancer treatment: enfortumab vedotin (EV), sacituzumab govitecan (SG), trastuzumab deruxtecan (DS-8201), and trastuzumab emtansine (T-DM1). This study delineates the safety profiles of ADC therapies for bladder cancer, confirming known risks and identifying potential new signals. The findings highlight the need for ADC-specific monitoring strategies and proactive management protocols to mitigate toxicities, thereby providing essential evidence for clinical decision-making."

Journal • Real-world evidence • Bladder Cancer • Candidiasis • Dermatology • Genito-urinary Cancer • Metabolic Disorders • Oncology • Solid Tumor

Understanding the Impact of Cost-Effectiveness Evaluations on Drug Pricing in Japan: A Case Study of Oncology Therapies (ISPOR-EU 2025) - "Eight oncology therapies (Kymriah, Epikinly, Cabometyx, Retevmo, Enhertu, Polivy, Darzquro, Padcev) have completed HTA reports published on the C2H platform. Japan's HTA system actively uses CEA to reassess high-cost oncology drugs. Although several products faced price revisions, the scope and consistency of these impacts vary. Manufacturers must understand the evolving regulatory, reimbursement, and HTA interplay to navigate Japan's market successfully."

Case study • Clinical • Cost effectiveness • HEOR • Pricing

Antibody-Drug Conjugates in Urothelial, Prostate, and Renal Cell Cancers: A Review of Current and Emerging Therapies. (PubMed, Crit Rev Oncol Hematol) - "Recent trials demonstrate encouraging outcomes with ADC such as Enfortumab Vedotin (EV), Sacituzumab Govitecan (SG), Trastuzumab Deruxtecan (T-DXd), and Disitamab Vedotin (DV) in UC, improving response rates and Progression-Free Survival (PFS). In RCC, ADC against ENPP3, CD70, and TIM-1 show durable responses in early trials, though challenges such as dose-limiting toxicities require further investigation. Overall, this review underscores ADC as a transformative approach in uro-oncology, highlighting ongoing advancements in combination strategies and biomarker-driven applications to refine therapeutic outcomes and expand treatment options for these challenging malignancies."

IO biomarker • Journal • Review • Genito-urinary Cancer • Oncology • Prostate Cancer • Renal Cell Carcinoma • Solid Tumor • Urethral Cancer • Urothelial Cancer • CD276 • CD70 • KIM1 • NECTIN4

P-EVOLUTION: Peripheral Neuropathy in Patients Receiving Enfortumab Vedotin and Pembrolizumab as First Line Treatment for Metastatic or Locally Advanced Urothelial Carcinoma (clinicaltrials.gov) - P=N/A | N=80 | Recruiting | Sponsor: LMU Klinikum | Trial completion date: Oct 2026 ➔ Feb 2027 | Trial primary completion date: Jul 2026 ➔ Dec 2026

Trial completion date • Trial primary completion date • Genito-urinary Cancer • Oncology • Pain • Solid Tumor • Urothelial Cancer

European Medicines Agency Validates Type II Variation Application for PADCEV (enfortumab vedotin) with KEYTRUDA (pembrolizumab) for Certain Patients with Muscle-Invasive Bladder Cancer (Astellas Press Release) - "The Type II variation application is based on results from the Phase 3 EV-303 clinical trial (also known as KEYNOTE-905)....The EMA’s Committee for Medicinal Products for Human Use (CHMP) and subsequently the European Commission (EC) are expected to share their opinion and decision on the Type II variation application calendar year 2026."

CHMP • EMA approval • EMA filing • Bladder Cancer

RECIPE-B1: Therapeutic Plasma Exchange With Enfortumab Vedotin and Pembrolizumab for Treatment of Bladder Cancers (clinicaltrials.gov) - P2 | N=70 | Recruiting | Sponsor: Mayo Clinic | N=50 ➔ 70

Enrollment change • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer

Clinical and histopathological features of alopecia associated with enfortumab vedotin treatment. (PubMed, J Eur Acad Dermatol Venereol) - No abstract available

Journal • Alopecia • Immunology • Oncology

Safety of Combining Radiation Therapy and Antibody Drug Conjugates in Advanced Urothelial and Other Cancers. (PubMed, Adv Radiat Oncol) - "Antibody drug conjugates (ADCs) such as enfortumab vedotin and sacituzumab govitecan are novel treatments increasingly used for metastatic urothelial carcinoma. This retrospective study thus found no added safety events for patients receiving RT with ADCs, even when administered concurrently. Further data to validate these findings is needed as the use of both ADCs and RT increases in patients with urothelial carcinoma."

Journal • Oncology • Solid Tumor • Urothelial Cancer

Cost-effectiveness analysis of enfortumab vedotin and pembrolizumab versus chemotherapy for patients with untreated advanced urothelial cancer in the United Kingdom. (PubMed, BMJ Open) - "In this economic model analysis, EV-Pem is not cost-effective compared with first-line chemotherapy in the UK, and a price reduction may be necessary."

HEOR • Journal • Genito-urinary Cancer • Oncology • Solid Tumor • Urethral Cancer • Urothelial Cancer