Javlor (vinflunine) / Pierre Fabre - LARVOL DELTA

Real-world treatment in patients with advanced urothelial carcinoma (aUC) after first-line (1L) platinum-based chemotherapy (PBC) and progression on avelumab 1L maintenance (Ave 1LM) in Germany: results of a retrospective observational study (CONVINCE PLUS) (DGHO 2025) - "2L treatment was enfortumab vedotin (EV) in 41 patients (74.5%), carboplatin + gemcitabine in 7 (12.7%), vinflunine in 6 (10.9%), and docetaxel in 1 (1.8%). This retrospective study describes patient characteristics and treatment patterns in patients with aUC who received 2L treatment after progression on 1L PBC and Ave 1LM in Germany since April 2022. EV was the most frequent 2L treatment in this population."

HEOR • Metastases • Observational data • Real-world • Real-world evidence • Retrospective data • Oncology • Primary Biliary Cholangitis • Solid Tumor • Urology • Urothelial Cancer

Impact of dose reductions on the efficacy of erdafitinib (Erda) in patients (Pts) with advanced or metastatic urothelial carcinoma (mUC): A post-hoc analysis of the phase III THOR study cohort-1 evaluating Erda versus chemotherapy (Chemo) (ESMO 2025) - P3 | "Methods Pts with advanced/mUC with FGFR3/2 alterations, ECOG PS 0–2, who progressed after 1–2 prior therapy (including anti-PD-[L]1) were randomized 1:1 to erda (8 mg per day with option of uptitration to 9 mg on day 14) or investigator's choice of chemo (docetaxel or vinflunine). Table: 3092P ERDA Randomized population ERDA Safety population a Number of dose reductions 0 1 ≥2 n 136 66 33 36 OS Median (95% CI), mo 12.1 (10.3, 16.4) 10.0 (8.1, 10.9) 10.3 (8.5, 16.8) 23.3 (18.2, NE) 6-mo rate, % 85 77 87 97 12-mo rate, % 51 36 43 81 Median PFS (95% CI), mo 5.6 (4.4, 5.7) 4.2 (2.8, 5.4) 5.6 (4.0, 5.9) 10.8 (5.8, 13.7) Confirmed ORR, n (%) 62 (45.6) 13 (19.7) 16 (48.5) 19 (52.8) a All randomized pts who received ≥1 dose of Erda. Conclusions Dose reductions of Erda due to TEAEs were common and did not seem to impact efficacy, highlighting the importance of proactive toxicity management to optimize both tolerability and clinical outcomes."

Clinical • Metastases • P3 data • Retrospective data • Oncology • Solid Tumor • Urothelial Cancer • FGFR3

Artificial intelligence-generated, explainable therapy recommendations for urothelial and renal cell carcinomas as support for multidisciplinary tumor conferences: AI development and first results from the KITTU project (DGU 2025) - "Recommendation UC Class (Number) UCF1-score NCC Class (Number) NCCF1-score High-Level Drug Tumor Therapy (59) Surgery (48) Follow-up (18) Best Supportive Care (9) Other (22) CatBoost TOTAL (156) 0.828 10.80 36 0.55 56 0.25 000.42 6 20.69 91 Drug Tumor Therapy (45) Follow-up (22) Radiotherapy (12) Surgery (10) Best Supportive Care (4) CatBoost TOTAL (93) 0.92 3 10.88 000.47 0.45 45 0.00 76 44 Low-Level: Surgery Radical Cystectomy (32) Re-TUR-B (10)Nephroureterectomy (3)Metastasectomy (1)Other (2)XGBoost TOTAL (48) 0.861 10.615 41.0000 1.00000 50000 8064Metastasectomy (5)Primary resection (4)Local recurrence resection (1)SoftOrdering TOTAL (10) 0.727 30.666 70.00 6303Low-Level: Drug-Based Tumor TherapyGemcitabine/Platinum (31)Pembrolizumab (9)Intravesical (BCG, Mitomycin) (8)Vinflunine (4)Paclitaxel (2)Enfortumab Vedotin (1)Atezolizumab (1)Nivolumab (1)Other (5)XGBoost TOTAL (62)0.87880.70000.93330.60000.01.0000.00.00.16670.7297Sunitinib (8)Nivolumab (7)Cabozantinib..."

Genito-urinary Cancer • Oncology • Prostate Cancer • Renal Cell Carcinoma • Solid Tumor • Urothelial Cancer

A Study to Evaluate Enfortumab Vedotin Versus (vs) Chemotherapy in Subjects With Previously Treated Locally Advanced or Metastatic Urothelial Cancer (EV-301) (clinicaltrials.gov) - P3 | N=608 | Active, not recruiting | Sponsor: Astellas Pharma Global Development, Inc. | Trial completion date: Aug 2025 ➔ Nov 2025

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

TROPiCS-04: Study of Sacituzumab Govitecan Versus Physician's Choice of Treatment in Participants With Urothelial Cancer That Cannot Be Removed or Has Spread (clinicaltrials.gov) - P3 | N=712 | Completed | Sponsor: Gilead Sciences | Active, not recruiting ➔ Completed

Trial completion • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer

Isothiocyanate-derived mercapturic acids potentiate tubulin polymerization inhibitors anticancer activity in urinary bladder cancer models (in vitro and in vivo studies) (EACR 2025) - "The metabolism of isothiocyanates via the mercapturic acid pathway leads to the formation of biologically active isothiocyanate-derived mercapturic acids, which accumulate at high concentrations in urine and urinary bladder tissue, making them particularly relevant for bladder cancer treatment.Material and A set of tubulin polymerization modulators (e.g., vinorelbine, colchicine, paclitaxel, combretastatin A4) was tested in vitro with structurally different mercapturic acids...The most promising combinations were further evaluated in vivo using orthotopic cancer models established by ultrasound-guided cancer cell inoculation.Result and Our in vitro studies demonstrated for the first time that mercapturic acids synergistically enhance the antiproliferative activity of microtubule polymerization inhibitors (such as colchicine, vinflunine, and combretastatin A4), but not microtubule stabilizers (such as paclitaxel)... These findings suggest that mercapturic acids enhance..."

Preclinical • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

Erdafitinib versus Chemotherapy in Fibroblast Growth Factor Receptor-Altered Advanced or Metastatic Urothelial Cancer After Progression on Anti-programmed Death-(Ligand) 1 Therapy: An Exploratory Analysis of the Asian Subpopulation in the THOR Phase 3 Study. (PubMed, Clin Genitourin Cancer) - "Erdafitinib showed improved survival compared with chemotherapy, with no new safety concerns in the Asian subpopulation. These findings were consistent with those for the overall study population in THOR Cohort 1 who received prior anti-PD-(L)1 therapy."

Journal • P3 data • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer • FGFR

A Study to Evaluate Enfortumab Vedotin Versus (vs) Chemotherapy in Subjects With Previously Treated Locally Advanced or Metastatic Urothelial Cancer (EV-301) (clinicaltrials.gov) - P3 | N=608 | Active, not recruiting | Sponsor: Astellas Pharma Global Development, Inc. | Trial completion date: Apr 2025 ➔ Aug 2025

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

Rapid quantification and classification of five vinca alkaloids used in cancer therapy by flow injection analysis with UV detection and chemometrics. (PubMed, Anal Methods) - "The study focused on vinca alkaloids: vinblastine, vincristine, vindesine, vinflunine, and vinorelbine, in the form of commercially diluted solutions in 0.9% NaCl at therapeutic concentrations. FIA-UV achieved 100% sensitivity and specificity in discriminating the five alkaloids, demonstrating non-inferiority to HPLC-UV. This method offers a streamlined workflow, reduces iatrogenic risk, and is well suited for antineoplastic agent preparation environments."

Journal • Oncology

Sacituzumab govitecan in advanced urothelial carcinoma: TROPiCS-04, a phase III randomized trial. (PubMed, Ann Oncol) - P3 | "SG did not result in a significant improvement in OS or PFS compared with TPC in pretreated aUC, although SG activity was demonstrated by a higher ORR. Early toxicity-related complications with SG may have impacted efficacy outcomes."

Journal • P3 data • Bladder Cancer • Febrile Neutropenia • Genito-urinary Cancer • Hematological Disorders • Infectious Disease • Neutropenia • Oncology • Solid Tumor • Urothelial Cancer

TROPiCS-04: Study of Sacituzumab Govitecan Versus Physician's Choice of Treatment in Participants With Urothelial Cancer That Cannot Be Removed or Has Spread (clinicaltrials.gov) - P3 | N=696 | Active, not recruiting | Sponsor: Gilead Sciences | Trial completion date: Jul 2025 ➔ Oct 2025 | Trial primary completion date: Jul 2025 ➔ Oct 2025

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

TROPiCS-04, a randomized phase III study of sacituzumab govitecan (SG) vs chemotherapy (CT) in pretreated advanced urothelial carcinoma (aUC): Overall survival (OS) and safety analysis (ESMO Asia 2024) - P3 | "Methods Pts with aUC who received prior platinum (PT)-based CT and checkpoint inhibitor therapy were randomized 1:1 to receive SG 10 mg/kg intravenously (IV) on days (D) 1 and 8 of 21-D cycles or treatment (tx) of physician's choice (TPC; paclitaxel 175 mg/m 2 IV, docetaxel 75 mg/m 2 IV, or vinflunine 320 mg/m 2 IV, on D1 of 21-D cycles). Safety data were consistent with the known toxicity profile of SG across tumor types, except for increased rates of neutropenic complications in this high-risk population. These AEs may have impacted overall results and could possibly be mitigated by increasing use of primary G-CSF prophylaxis."

Clinical • Late-breaking abstract • Metastases • P3 data • Oncology • Solid Tumor • Urothelial Cancer

Enhancing mesothelin-CAR T cell efficacy in ovarian cancer: the role of drug combinations (SITC 2024) - "Specifically, the conventional chemotherapeutic agent cisplatin and the antimetabolite cytarabine significantly enhanced the cytotoxic activity of MBBz CAR T cells but not M28z cells. Conversely, idarubicin augmented the efficacy of M28z CAR T cells but did not enhance the activity of MBBz cells (figure 2).Furthermore, several drugs were observed to enhance the efficacy of CAR T therapy across both constructs, including the vinca alkaloid vinflunine, the antimetabolite gemcitabine, and the PARP inhibitor rucaparib (figure 2)...Specific drugs showed CAR construct-dependent enhancement, while others were effective across both constructs. These findings can be explored further to create personalized synergistic opportunities, improving treatment outcomes."

CAR T-Cell Therapy • Clinical • Hematological Malignancies • Oncology • Ovarian Cancer • Solid Tumor • MSLN

Real-world data on treatment patterns and guideline adherence in patients with locally advanced and metastatic urothelial bladder cancer (la/mUC) in Germany (EMUC 2024) - "During the study period national and international guidelines recommended platinum-based chemotherapy (PBC) as the standard treatment for la (T4b or ≥N2) or mUC (M1), with cisplatin being more effective than carboplatin...Overall 29% of pts with PBC received maintenance with avelumab. 70 pts (15%) were systemically pre-treated and 116 pts (25%) received 2L treatment, 61% ICI, 28% ADC, 6% PBC, and 4% vinflunine...PD-L1 testing was not performed in 35% of the pt- population. Altogether, there is a considerable proportion of untreated patients."

Adherence • Clinical • Metastases • Real-world • Real-world evidence • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urology • Urothelial Cancer

A Study to Evaluate Enfortumab Vedotin Versus (vs) Chemotherapy in Subjects With Previously Treated Locally Advanced or Metastatic Urothelial Cancer (EV-301) (clinicaltrials.gov) - P3 | N=608 | Active, not recruiting | Sponsor: Astellas Pharma Global Development, Inc. | Trial completion date: Aug 2024 ➔ Feb 2025

Metastases • Trial completion date • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer

TROPiCS-04: Study of Sacituzumab Govitecan Versus Physician's Choice of Treatment in Participants With Urothelial Cancer That Cannot Be Removed or Has Spread (clinicaltrials.gov) - P3 | N=696 | Active, not recruiting | Sponsor: Gilead Sciences | Trial completion date: Oct 2024 ➔ Jul 2025 | Trial primary completion date: Oct 2024 ➔ Jul 2025

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

Matching-Adjusted Indirect Comparison of the Efficacy and Safety of Erdafitinib vs Enfortumab Vedotin in Patients with Locally Advanced Metastatic Urothelial Carcinoma. (PubMed, J Health Econ Outcomes Res) - P3 | " An anchored MAIC was conducted according to the National Institute for Health and Care Excellence Decision Support Unit guidance, with physician's choice of chemotherapy (docetaxel/paclitaxel and vinflunine) as the common comparator. The MAIC indicates comparable efficacy of erdafitinib vs EV for overall survival and progression-free survival, with erdafitinib showing a higher probability of achieving deep responses. While erdafitinib is associated with slightly more adverse events compared with EV, these events seem to be less severe."

Journal • Metastases • Oncology • Solid Tumor • Urothelial Cancer • FGFR

Paradigm shift in systemic therapy for metastatic urothelial carcinoma-antibody-drug conjugates (ADCs) and fibroblast growth factor receptor (FGFR) inhibitors (PubMed, Urologie) - "These novel combinations are revolutionizing the treatment standard for metastatic urothelial carcinoma and necessitate a new approach to managing side effects."

Journal • Metastases • Review • Oncology • Solid Tumor • Urothelial Cancer • FGFR

Impact of Prior Chemotherapy on Response to Second-line Pembrolizumab in Urothelial Cancer: Exploratory Analysis of the Phase 3 KEYNOTE-045 Trial. (PubMed, Eur Urol) - "When compared with chemotherapy, prolonged OS and durable responses to second-line pembrolizumab were observed independently of the response to or type of prior platinum-based chemotherapy. These findings further support pembrolizumab as second-line treatment for advanced UC."

Journal • P3 data • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer

Phase 3 THOR Japanese subgroup analysis: erdafitinib in advanced or metastatic urothelial cancer and fibroblast growth factor receptor alterations. (PubMed, Int J Clin Oncol) - P3 | "In the Japanese subgroup, erdafitinib showed improved survival and response compared to chemotherapy, with no new safety concerns. These results support erdafitinib as a treatment option for Japanese mUC patients with FGFR alterations, and early FGFR testing after diagnosis of mUC should be considered."

Journal • Metastases • P3 data • Genito-urinary Cancer • Oncology • Oral Cancer • Solid Tumor • Urothelial Cancer • FGFR

FGFR3-mutated urothelial carcinoma of bladder and upper tract including ureter and renal pelvis: A comparative genomic profiling study. (ASCO 2024) - "THOR-1 trial showed a significant overall survival benefit with erdafitinib (FGFR inhibitor) vs chemotherapy (taxane or vinflunine) in patients with advanced urothelial carcinoma of the bladder (UCB) or upper tract urothelial carcinoma (UTUC). Although histologically similar, the genomic landscape of FGFR3mut+ RPUC and UUC has notable differences with FGFR3mut+ UCB. Limitations include lack of clinical data annotation, inherent selection biases, and the retrospective nature of this work. Findings may impact clinical trial designs for UCB and UTUC, including evaluating combinations of anti-FGFR3 with other agents."

IO biomarker • Tumor mutational burden • Bladder Cancer • Oncology • Solid Tumor • Urothelial Cancer • FGFR3 • HER-2 • KDM6A • MSI • MTAP • PD-L1 • PIK3CA • PTEN • TSC1

THOR: A Study of Erdafitinib Compared With Vinflunine or Docetaxel or Pembrolizumab in Participants With Advanced Urothelial Cancer and Selected Fibroblast Growth Factor Receptor (FGFR) Gene Aberrations (clinicaltrials.gov) - P3 | N=629 | Active, not recruiting | Sponsor: Janssen Research & Development, LLC | Trial completion date: Sep 2024 ➔ Nov 2026

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

Use of early dynamics of clinical and laboratory parameters to predict resistance in patients with metastatic urothelial carcinoma receiving post-platinum atezolizumab (AACR 2024) - "We investigated readily available baseline and EOT variables from the phase 3 clinical trial IMvigor211, which compared atezolizumab, a PD-L1 inhibitor, with chemotherapy (taxane or vinflunine), in patients with mUC who have progressed on platinum-based chemotherapy. Of 931 patients in IMvigor211, 902 were evaluable for our analysis...The strongest baseline predictors are PD-L1 expression, prior treatment with both cisplatin and carboplatin, and the presence of liver metastases... Our prediction models employing readily available and affordable EOT clinical and laboratory variables robustly (AUC 0.83) identified patients with early resistance and may inform patient-specific therapeutic decisions. Further validation is required."

Clinical • IO biomarker • Metastases • Oncology • Solid Tumor • Urothelial Cancer

THOR: A Study of Erdafitinib Compared With Vinflunine or Docetaxel or Pembrolizumab in Participants With Advanced Urothelial Cancer and Selected Fibroblast Growth Factor Receptor (FGFR) Gene Aberrations (clinicaltrials.gov) - P3 | N=629 | Active, not recruiting | Sponsor: Janssen Research & Development, LLC | Trial primary completion date: Feb 2024 ➔ Sep 2024

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

FGFR3 mutated (FGFR3mut+) urothelial carcinoma of bladder (UCB) or upper tract (UTUC): A comparative genomic landscape study. (ASCO-GU 2024) - "THOR trial showed a significant overall survival benefit with erdafitinib (FGFR inhibitor) vs (taxane or vinflunine) in patients (pts) with advanced UCB or UTUC. Although histologically similar, the genomic landscape of FGFR3mut+ UTUC has notable differences with FGFR3mut+ UCB. Limitations include lack of clinical data annotation. The findings may impact of clinical trial designs for UCB and UTUC, including evaluating combinations of anti-FGFR3 with other agents."

IO biomarker • Tumor mutational burden • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer • FGFR3 • FUS • HER-2 • MSI • MTAP • PIK3CA • PTEN • TSC1