tbuckley/cabot-search huggingface dataset:
Impact of relative dose intensity on efficacy of enfortumab vedotin monotherapy in platinum and ICI resistant metastatic urothelial carcinoma: A multi-institutional real-world analysis.
Authors: Yuki Endo, Yukihiro Kondo, Yuma Sakura, Go Kaneko, Nozomi Hayakawa, Daiki Ikarashi, Ryo Yamashita, Suguru Shirotake, Wataru Obara, Eiji Kikuchi
Journal: Journal of Clinical Oncology (2025)

728 Background: The treatment paradigm for metastatic or locally advanced urothelial carcinoma (mUC) has shifted towards combination therapies with Enfortumab Vedotin (EV) and Pembrolizumab. Understanding EV's characteristics is crucial for optimizing treatment. The EV-101 trial showed a correlation between exposure and efficacy, but few real-world studies explore how relative dose intensity (RDI) impacts outcomes. This study examines RDI's effect on efficacy using real-world data. Methods: We retrospectively analyzed 123 mUC patients treated with EV monotherapy as third-line or later, following progression after platinum-based chemotherapy and resistance to immune checkpoint inhibitors (ICIs). Data were collected from five institutions. We evaluated overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). Patients were grouped into full dose on-schedule (FDO) and dose/schedule adjusted (DSA) based on EV dose and timing until best response (BR). On DSA group, relative dose intensity (RDI) until BR (BRRDI) was measured, and patients were classified into High (BRRDI &gt; 80), Intermediate (80 ≥ BRRDI &gt; 70), and Low (BRRDI ≤ 70) groups for comparison. Results: Among the 123 patients, median OS (mOS) was 14.8 Ms, median PFS (mPFS) was 7.1 Ms, and ORR was 48%, with a complete response (CR) rate of 9%. In the FDO group (31 patients), mOS was 9.3 Ms, mPFS was 4.5 Ms, and ORR was 29% (CR: 0%). In the DSA group (93 patients), mOS was 17.1 Ms (p=0.002), mPFS was 8.8 Ms (p=0.019), and ORR was 56% (CR: 12.1%) (p=0.0029 for ORR, p=0.017 for CR). In the BRRDI analysis, median time to BR was 2.6 Ms. ORR for High, Intermediate, and Low groups were 50% (CR: 20%), 58% (CR: 3.4%), and 63% (CR: 9.4%), respectively, with significant differences in CR (p=0.026). Conclusions: Patients requiring dose or schedule adjustments before best response showed better ORR, OS, and PFS than those on full dose. Higher BRRDI correlated with better CR, emphasizing the need to manage adverse events while maintaining dose intensity until BR.
Efficacy and toxicity profile of antibody-drug conjugate (ADC) based combination therapy in patients with advanced urothelial carcinoma (aUC): A systematic review of clinical trials.
Authors: Salvador Jaime-Casas, Miguel Zugman, Regina Barragan-Carrillo, Peter D. Zang, Hedyeh Ebrahimi, Benjamin Mercier, Daniela V. Castro, Wesley Yip, Xiaochen Li, Nazli Dizman, Nicholas Salgia, Joann Hsu, Charles B Nguyen, Alex Chehrazi-Raffle, Zeynep Busra Zengin, Luis A Meza, Sumanta Kumar Pal, Abhishek Tripathi
Journal: Journal of Clinical Oncology (2025)

813 Background: ADCs have revolutionized the treatment landscape of aUC and are being evaluated as part of combination regimens with checkpoint inhibitors (CPI) or other ADCs. We sought to evaluate the efficacy and safety/tolerability profile of ADC-based combination therapy in aUC. Methods: We systematically searched the PubMed and Embase databases for published prospective clinical trials through July 2024. Peer-reviewed clinical trials evaluating ADCs as part of a combination regimen in aUC were included. We extracted safety and efficacy outcomes, including objective-response rate (ORR), any-grade adverse events (AEs), and grade ≥3 AEs. We excluded reviews, editorials, retrospective studies, and case reports. Two independent reviewers screened titles and abstracts for relevance, followed by a full-text review to confirm eligibility. Results: 627 evaluable patients from 5 prospective trials investigating enfortumab vedotin or sacituzumab govitecan were identified. Overall, we recorded an ORR of 66.2%. 366 patients across all studies experienced ≥ grade 3 AEs, for a risk rate (RR) of 58.4%. By using a random-effects model, the pooled RR for AEs (Grade≥3) was 61% (95% CI, 52%–69%; P=0.18; Table). The most common grade ≥3 AEs were neutropenia (RR 0.14 [95% CI 0.04- 0.40]), anemia (RR 0.10 [95% CI 0.03-0.30]), and maculopapular rash (RR 0.10 [95% CI 0.04-0.23]). Distribution of specific AEs varied significantly based on regimen, with a higher incidence of ≥grade 3 anemia, neutropenia, and diarrhea in SG-based combinations (SG+ EV and SG+ CPI). Conclusions: While ADC-based combination regimens show promising responses, they also have high rates of AEs in patients with aUC. Further clinical trials evaluating these combination regimens are crucial to further optimize the role of ADCs in this disease setting. Safety/tolerability profile for any grade and grade ≥3 AEs. Toxicity Any Grade Grade≥3 Risk rate, 95% CI Risk rate, 95% CI Anemia 0.31 [0.09; 0.66] 0.10 [0.03; 0.30] Neutropenia 0.24 [0.05; 0.65] 0.14 [0.04; 0.40] Diarrhea 0.51 [0.19; 0.82] 0.07 [0.02; 0.17] Peripheral sensory neuropathy 0.50 [0.47; 0.54] 0.03 [0.02; 0.05] Fatigue 0.45 [0.26; 0.65] 0.06 [0.03; 0.13] Maculopapular rash 0.36 [0.26; 0.47] 0.10 [0.04; 0.23]
Treatment patterns and survival in men with metastatic castration-resistant prostate cancer (mCRPC): A systematic literature review of 35 real-world observational studies.
Authors: Amit D Raval, Viji Queen V, Matthew J. Korn, Vanessa Quintero, Stephen J. Freedland
Journal: Journal of Clinical Oncology (2025)

101 Background: Treatment landscapes have changed dramatically in prostate cancer in the past decade. Therapies like androgen receptor pathways inhibitors (ARPIs), which were initially approved for mCRPC are now approved in the earlier disease spectrum, including biochemical recurrence (BCR), non-metastatic castration-resistant prostate cancer (nmCRPC), and hormone-sensitive metastatic prostate cancer (mHSPC). Further, several other life-prolonging therapies, including radiopharmaceuticals, immunotherapies, and poly-ADP ribose polymerase inhibitors (PARPi), have been approved for mCRPC in the last decade. Given these changes, this systematic literature review (SLR) aimed to summarize treatment patterns and survival in patients with mCRPC. Methods: Electronic databases (PubMed, Embase) and key conferences (2022-2024) were searched systemically for real-world (RW) observational studies published between Jan 2015 and March 2024 that examined treatment patterns and survival in patients with mCRPC. A GenAI-powered literature review platform assisted in study selection alongside human validation, and independent reviewers extracted and assessed the data for narrative synthesis of key findings. Results: From 4,565 retrieved citations, 35 studies with a total of 86,131 patients with mCRPC met inclusion criteria. In most studies, patient median age ranged from 65 to 75. Studies predominantly utilized electronic medical records (EMR)/chart review (n=24), followed by a registry/-linked claims (n=10). Most studies were from North America (n=21; 18 United States; 3 Canada), followed by Europe (n=6), Asia (n=3), Oceania (n=3), and others (n=2). Bone and visceral metastases were present in ≥ 70% of mCRPC and ≤30% in most studies, respectively. ARPI was the most frequently utilized first line of therapy(1L) for mCRPC in all studies (≥50% in most studies), followed by chemotherapy, albeit with varying magnitude by geographic regions. Chemotherapy for 1L mCRPC was more common in Europe and Oceania than in the US. The use of radiopharmaceuticals, PARPIs, and immunotherapy was low in most studies (&lt;10%) as 1L mCRPC. Most studies found ARPI to ARPI was the most common 1L to 2L mCRPC sequence, though in few studies, ARPI-chemotherapy was the common 1L to 2L mCRPC sequence. In most studies, median real-world overall survival ranged from 18 to 27 months and varied by genetic mutation status. Conclusions: Findings highlight that ARPI remained the most utilized 1L/2L in men with mCRPC, and back-to-back ARPI was also a common practice even after the availability of the other life-prolonging therapies. This SLR highlights the need to optimize treatment beyond systemic hormone therapy.
A phase III randomized trial of eribulin (E) with gemcitabine vs standard of care (SOC) for patients (pts) with metastatic urothelial carcinoma (mUC) refractory to or ineligible for PD/PDL1 antibody (Ab): SWOG S1937—Updated design.
Authors: Sarmad Sadeghi, Samuel Callis, Primo N Lara, Stephanie A. Berg, Jason Robert Brown, Rick Bangs, Darrell Nakagawa, Siamak Daneshmand, None Ian Murchie Jr., Thomas W. Flaig, Daniel P. Petrylak, Seth P. Lerner
Journal: Journal of Clinical Oncology (2025)

TPS887 Background: UC is the 2nd most common genitourinary cancer. Enfortumab vedotin (EV) + pembrolizumab became a SOC in 2023 in frontline mUC setting. There is not established standard of care for the subsequent lines of therapy limiting treatment options to platinum-based chemotherapy, docetaxel, paclitaxel, gemcitabine, or Sacituzumab govitecan monotherapy. Erdafitinib remains an option for pts with FGFR3 alterations. A phase I/II CTEP study of eribulin (E) for mUC established the activity of E with an objective response rate (ORR) of 37.5%, median progression-free survival (PFS) of 4.1 months (mo), and median overall survival (OS) of 9.5 mo (N=150). A phase II CTEP study of gemcitabine-eribulin (GE) in cisplatin ineligible mUC showed an ORR of 50%, median OS of 11.9 mo, and median PFS of 5.3 mo (N=24). The most common Grade 3-4 toxicities included neutropenia (63%), anemia and fatigue (29% each). Pts with liver metastases benefited from therapy with an ORR of 71% (n=7) for GE vs. 24% for E (N=49). This trial has now been amended to account for first-line treatment changes and to include SG as a control arm option. In this amendment the eribulin alone arm was closed to simplify the design and reduce the sample size. Methods: This is an updated phase III, randomized trial comparing GE vs. SOC (SG, docetaxel, paclitaxel, or gemcitabine monotherapy). E is given at 1.4mg/m2 on day (D) 1 and 8 of a 21 D cycle. Gemcitabine is added to E at 1000 mg/m2 on D 1 and D 8. SOC follows approved dosing. There is no limit to the number/sequence of prior regimens. All pts must have: received systemic therapy with EV; received PD1/PDL1 Ab or be deemed ineligible for PD1/PDL1 Ab. The study seeks to find at least a 50% increase in the primary endpoint of OS (Hazard Ratio (HR) = 0.667). Secondary endpoints include ORR and PFS. This design has a power of 80% and a one-sided alpha of 0.05 to detect a HR=0.667. We require 92 pts in each arm for a total of 168 eligible pts. The amended and restructured study was approved in January of 2024. Funding: National Institutes of Health/National Cancer Institute grants U10CA180888, U10CA180819. Eribulin is provided by Eisai. Clinical trial information: NCT04579224 .
Phase 1/2 INTerpath-005 study: V940 (mRNA-4157) plus pembrolizumab with or without enfortumab vedotin (EV) for resected high-risk muscle-invasive urothelial carcinoma (MIUC).
Authors: Guru P. Sonpavde, Begoña P. Valderrama, Karim Chamie, Shilpa Gupta, Maria De Santis, Joydeep K. Banerjee, Laureen Ojalvo, Yixin Ren, Abhishek Bavle, Thomas Powles
Journal: Journal of Clinical Oncology (2025)

TPS893 Background: It is hypothesized that V940 (mRNA-4157), an individualized neoantigen therapy consisting of an mRNA encoding up to 34 tumor neoantigens, will work in synergy with immune checkpoint inhibitors by generating de novo tumor-specific T-cell activity. In a phase 2 trial of patients with high-risk melanoma, adjuvant V940 + pembrolizumab had a manageable safety profile and improved recurrence-free and distant metastasis–free survival versus pembrolizumab monotherapy. The phase 1/2 INTerpath-005 study (NCT06305767) has 2 cohorts. The phase 1 open-label, single-arm perioperative cohort will evaluate perioperative (neoadjuvant and adjuvant) V940 + pembrolizumab + EV for muscle-invasive bladder cancer (MIBC). The phase 2 double-blind, randomized adjuvant cohort will evaluate adjuvant V940 + pembrolizumab versus placebo + pembrolizumab for high-risk MIUC. Methods: Eligibility criteria for the perioperative cohort include age ≥18 years, diagnosis of MIBC (T2-T4aN0M0 or T1-T4aN1M0) with urothelial carcinoma histology, eligibility and willingness to undergo radical cystectomy (RC) + pelvic lymph node dissection (PLND), and cisplatin ineligibility. Eligibility criteria for the adjuvant cohort include age ≥18 years, diagnosis of MIUC with predominant UC histology, radical resection ≤7 weeks before providing informed consent and ≤14 weeks before randomization, high-risk pathologic disease (ypT2-4a and/or ypN+ after neoadjuvant chemotherapy [NAC]; pT3-4a and/or pN+ without NAC), and cisplatin ineligibility. In the perioperative cohort, approximately 30 patients will receive neoadjuvant pembrolizumab 200 mg IV on day 1 Q3W × 4 cycles + EV 1.25 mg/kg IV on days 1 and 8 Q3W × 4 cycles + V940 1 mg IM on day 1 Q3W × 1-4 doses. Patients will undergo RC + PLND followed by adjuvant pembrolizumab 200 mg IV on day 1 Q3W × 13 cycles + EV 1.25 mg/kg IV on days 1 and 8 Q3W × 5 cycles + V940 1 mg IM on day 1 Q3W × 5-8 doses, depending on number of doses administered in neoadjuvant period, for a total of 9 doses. In the adjuvant cohort, approximately 200 patients will be randomly assigned 1:1 to receive pembrolizumab 400 mg IV Q6W × 9 cycles + V940 1 mg IM Q3W × 9 doses or pembrolizumab 400 mg IV Q6W x 9 cycles + placebo IM Q3W x 9 doses. Randomization in the adjuvant cohort will be stratified by circulating tumor DNA status at screening (positive vs negative vs not evaluable) and prior NAC (yes vs no). The primary end points are safety (perioperative cohort) and DFS per investigator assessment (adjuvant cohort). Secondary end points are pathologic complete response and pathologic downstaging (perioperative cohort); overall survival, distant metastasis–free survival per investigator, safety, and tolerability (adjuvant cohort). Clinical trial information: NCT06305767 .
Real-world evidence for factors associated with development of castration-resistant prostate cancer (CRPC).
Authors: Charles J. Ryan, Kristine Peregrino Lacuna, Lena Yoo, Zuzanna Szmukier, Deborah M Boldt-Houle
Journal: Journal of Clinical Oncology (2025)

92 Background: Androgen deprivation therapy (ADT) is foundational for advanced prostate cancer (PCa); luteinizing hormone-releasing hormone (LHRH) agonists and gonadotropin-releasing hormone (GnRH) antagonists are widely used. ~20% of PCa patients on LHRH analogs develop castration-resistant prostate cancer (CRPC) within 3 years. We evaluated factors associated with CRPC onset and time to CRPC onset for agonists vs. antagonist using real-world dataset. Methods: Data were collected from an EMR database purchased from Decision Resources Group. Analysis set included PCa patients who received ≥1 ADT 1991-2020 and excluded those who received both LHRH agonist and a GnRH antagonist and/or developed CRPC on the same day/before ADT initiation. CRPC onset date was defined as the earlier of 2 options: CRPC diagnosis or first CRPC therapy (standard of care treatments e.g., androgen pathway inhibitors, immunotherapy, chemotherapy, radiotherapy). Associations between CRPC and each available factor were evaluated using MV Cox regression. Time to CRPC onset was assessed for agonists vs. antagonist. Results: 41,379 patients were analyzed. Factors associated with MV HR &gt;1.4, p&lt;0.001 were oncology setting, metastatic disease, absence of diabetes, and no statin use (Table 1). Antagonist use had an adjusted HR of 1.4 (95% CI 1.06-1.85, p=0.02). Median time to CRPC onset after ADT initiation is 10.9 months for antagonist (n=238) vs. 17.3 months for agonists (n=5,231). Conclusions: Treatment-related (oncology setting; antagonist use) and comorbidity factors (older age, no diabetes, no statin use) were associated with CRPC onset. Oncology setting and antagonist use may reflect practice patterns in higher risk individuals. The association between diabetes and CRPC risk is under further evaluation e.g., whether antecedent diabetes therapies confer protection. Hazard ratio (95% CI) and P-value of CRPC for top 10 significant factors 1 in multivariable analysis. Multivariable (n=9,554) 2,3 Factors HR (95% CI) P-value Oncology vs Urology (Setting) 3.04 (2.56-3.59) &lt;0.001 W vs W/o Metastasis (Baseline) 2.20 (1.58-3.05) &lt;0.001 W/o vs W Diabetes 4 1.45 (1.22-1.73) &lt;0.001 W/o vs W Statin 4 1.43 (1.25-1.63) &lt;0.001 Antagonist vs Agonist 1.40 (1.06-1.85) 0.02 W/o vs W Hypertension 4 (HTN) 1.17 (1.01-1.36) 0.041 Decreasing ADT Exposure per Year 1.09 (1.05-1.13) &lt;0.001 Increasing Age per Year (Older vs Younger) 1.02 (1.02-1.03) &lt;0.001 1 Significant for multivariable analysis. 2 Excluded patients with CRPC on the same day/before ADT Start. 3 Excluded patients with both agonist and antagonist use; without BMI, PSA, and age data; non-white/black race; with unknown urology/oncology or with both urology/oncology setting. 4 Has taken statins/hypertension/diabetes medication or diagnosed with hypertension/diabetes disease.
Efficacy and safety of disitamab vedotin combined with toripalimab as neoadjuvant treatment for patients with locally advanced muscle-invasive bladder cancer: A mono-institutional retrospective study.
Authors: Geng Zhang, Qiang Fu, Fuxun Zhang, Fan Yang, Haozhong Hou
Journal: Journal of Clinical Oncology (2025)

726 Background: Currently, the efficacy of cisplatin-based neoadjuvant chemotherapy for patients with muscle-invasive bladder cancer (MIBC) is unsatisfied. Disitamab vedotin (RC48) as an antibody-drug conjugate is composed by a monoclonal antibody against human epidermal growth factor receptor 2 (HER2) and a cytotoxic agent monomethyl auristatin E. Although this drug was approved in 2021 for HER2-overexpressing gastric cancer, disitamab vedotin as mono- or combination regimen is in clinical development for treating other solid tumors now. This study aims to assess the safety and efficacy of disitamab vedotin combined with toripalimab as neoadjuvant treatment for patients with HER2 positive locally advanced MIBC. Methods: The data of patients with HER2 positive locally advanced MIBC who received combination therapy [disitamab vedotin (2.0mg/kg, iv, D 1 , Q3W) combined with toripalimab (240mg, iv, D 1 , Q3W) were collected retrospectively and analyzed. The primary endpoint was pathological complete response (pCR), and the secondary endpoints included objective response rate (ORR), overall survival (OS) and treatment-related adverse events (TRAEs). All outcomes were assessed by a blinded independent review committee. Results: The data of 20 included patients who received combination regimen from 2023 Jun to 2023 Sept were analyzed. Among them, the median age was 65 (47-86) years. The overall pCR was 79%, while the ORR was100%. The median PFS was 4.5 (2.45-9.6) months, and overall survival (OS) was not reached. The most common TRAEs were nausea (7,35.0%), alopecia (8,40.0%), and rash (3,15%). Only 1 patients reported Grade 3 TRAE (feeble), and no grade 4 TRAEs were observed. Conclusions: The safety and efficacy of neoadjuvant disitamab vedotin combined with toripalimab in patients with HER2 positive locally advanced MIBC were promising. This study will be verified in future.
Optimizing treatment approaches in nested bladder tumors: A multicenter retrospective study.
Authors: Patrizia Giannatempo, Paolo Ambrosini, Marco Maruzzo, Francesco Mistretta, Luigi Da Pozzo, Francesco Soria, Marco Barella, Alessandro Rametta, Alberto Quistini, Giovanni La Croce, David D'Andrea, Andrea Di Marco, Rodolfo Hurle, Roberto Contieri, Paolo Gontero, Gennaro Musi, Giuseppe Procopio, Rosalba Miceli, Alessio Polymeropoulos, Nicola Nicolai
Journal: Journal of Clinical Oncology (2025)

743 Background: Identifying optimal treatment strategies in nested bladder tumors is critical. This multicenter study aims at evaluating progression-free survival (PFS) end overall survival (OS) according to disease extent, presentation and treatment including Bacillus Calmette-Guérin (BCG), radical cystectomy (RC) and chemotherapy (CT). Methods: Data were collected from 61 patients with nested bladder tumors across 5 centers over a 10-year period (2013–2023). Patients were stratified according to 1) time of diagnosis of nested variant (disease onset Vs recurrence) 2) disease extent (NMIBC vs MIB, vs cN+ Vs M+) 3) treatment groups based on their initial treatment: ( BCG ± RC vs RC only Vs RC + CT). Kaplan-Meier analysis was used to assess median PFS (mPFS) and median OS (mOS), while p-values &lt;0.05 was used to determine statistical significance across groups. Results: The median follow-up was 30.6 months (95% CI: 16.4–40.6). At diagnosis 15 (24.6%) were NMIBC, 26 (42.6%) MIBC, 15 (24.6%) N+ and 5 (8.2%) metastatic (M). Of the 15 NMIBC 80% received initial BCG. Pts with nested bladder tumors at onset had worse PFS and OS (mPFS of 99.6 months (95% CI: 55.2-NR) and mOS of 107.3 months (95% CI: 71.6-NR) than those with nested bladder tumor at recurrence mPFS of NR (95% CI: 42.1-NR) and mOS 138.4 (95% CI: 51.7-NR). None of these differences were statistically significant. Patients with M and N+ stages showed a trend towards a worse prognosis than those with NMIBC and MIBC, with no statistically difference in mPFS and mOS between MIBC and NMIBC stages. According to treatment, the best mPFS and mOS were recorded among patients receiving RC and CT [mPFS 99.6 months (95% CI: 55.2-NR) and mOS of 107.3 months (95% CI: 107.3-NR)]. Those receiving BCG followed by RC group had a mPFS of 84.2 months (95% CI: 68.1-NR) and mOS of 85.9 months (95% CI: 71.6-NR) while those undergoing RC alone apparently had the worse mPFS of 42.1 months (95% CI: 42.1-NR) and mOS of 51.7 months (95% CI: 14.7.1-NR). None of these differences were statistically significant. Conclusions: This study represents the largest case series of nested bladder tumors. It suggests limited benefit from BCG treatment. Most patients had advance disease, most of NMIBC finally need CT. Diagnosis at recurrence and combination of RC and CT tend to better survivals. Analyses that are more detailed are ongoing to evaluate clinical benefits according to the different clinical features.