tbuckley/cabot-search huggingface dataset:
Kidney-sparing approach for selected localized high-risk upper tract urothelial carcinoma: A pilot study combining endoscopic thulium laser ablation with perioperative disitamab vedotin and immune checkpoint inhibitors.
Authors: Jianjun Ye, Zeyu Chen, Xinyang Liao, Xiang Tu, Qihao Wang, Lei Zheng, Kai Chen, Qiang Wei, Yige Bao
Journal: Journal of Clinical Oncology (2025)

791 Background: Radical nephroureterectomy (RNU) is the standard treatment for localized high-risk upper tract urothelial carcinoma (UTUC). However, the predominance of UTUC in elderly populations with significant comorbidities necessitates alternative treatment strategies that prioritize functional nephron preservation. This pilot study aims to assess the efficacy and safety of a comprehensive modality of kidney-sparing approach, comprising endoscopic Thulium laser ablation and perioperative systemic therapy (Disitamab vedotin [DV] and immune checkpoint inhibitors [ICIs]), in a carefully selected cohort of localized high-risk UTUC. Methods: This ongoing study, initiated in November 2021 at West China Hospital of Sichuan University, included selected patients with localized UTUC patients (cT≤2N0M0) characterized by conditions such as solitary kidney, bilateral tumors, impending/already renal insufficiency and individual refusal/ineligibility for RNU. The treatment protocol consisted of endoscopic biopsy and initial laser ablation, followed by 3-4 cycles of DV and ICIs administered every three weeks as induction therapy. Subsequently, patients underwent maximal endoscopic laser ablation. Those exhibiting efficient response received a 6-month course of DV and a 12-month course of ICIs as maintenance therapy. Co-primary endpoints were 1-yr disease-free survival (DFS) and conversion-free survival (CFS). Secondary endpoints included clinical complete response (cCR) rate, renal function benefits, and treatment safety. Results: Thirty-two patients were enrolled, with a median follow-up of 15 months. The majority of patients (26/32, 81.25%) were diagnosed with HER2-positive in biopsy-related IHC, including 3 cases of HER2 3+ and 23 cases of HER2 2+. During the follow-up, 17 local recurrences were observed in 10 patients and the 1-yr DFS rate was 68.75%. HER2 status was a significant predictive factor for local recurrence (OR, 0.15; 95% CI, 0.03, 0.91). Salvage RNU was performed in 2 patients, yielding a 1-yr CFS rate was 93.75%. The cCR rate is 78.13% (25/32). Postoperative renal function impairment was noted in 6 patients (18.75%). Mean eGFR improvements (ml/min/1.73m2) were observed with 3.15 at 1 month, 5.07 at 3 months, 2.41 at 6 months, and 3.97 at 12 months. Notably, no grade 3 or higher systemic toxicities were observed. Conclusions: Preliminary findings indicate that the combination of endoscopic Thulium laser ablation with perioperative systemic therapy (DV and ICIs) demonstrated promising efficacy and manageable safety in selected patients with localized high-risk UTUC. These results provide a solid foundation for the ongoing phase 2 trial (WUTSUP-03) and suggest a potential paradigm shift in the management of this challenging patient population.
Impact of perioperative acute kidney injury on future renal outcomes in patients who undergo radical cystectomy: A multi-institutional retrospective cohort study.
Authors: Naoki Fujita, Shogo Hosogoe, Toshikazu Tanaka, Noritaka Ishii, Masaki Momota, Hiroyuki Ito, Takahiro Yoneyama, Chikara Ohyama, Shingo Hatakeyama
Journal: Journal of Clinical Oncology (2025)

879 Background: Acute kidney injury (AKI) is one of the frequent complications in patients who undergo radical cystectomy (RC). Although AKI has been reported to have a negative impact on renal outcomes in several diseases, the impact of perioperative AKI on major adverse kidney events (MAKE) in patients who undergo RC remains unclear. Methods: This multi-institutional retrospective cohort study included 702 patients with muscle invasive bladder cancer who underwent RC. AKI was defined according to the KDIGO criteria. Patients were divided into two groups: patients who developed AKI after RC (AKI group) and patients who did not (non-AKI group). MAKE was a composite of sustained ≥50% decline in eGFR, doubling of serum creatinine from the baseline, and sustained decrease in eGFR to &lt;15 ml/min/1.73m 2 . The laterality and grade of hydronephrosis at the time of MAKE onset or last follow-up were evaluated. Multivariable Cox-proportional hazards regression analysis was performed to evaluate the impact of perioperative AKI on MAKE-free survival. Results: The median age and follow-up period were 70 years and 48 months, respectively. Of the 702 patients, 368 (52%) developed AKI after RC, with 26% having severe AKI (stage 2-3). Significant declines in eGFR at one-, three, and five-year after RC were observed in the AKI group compared with those in the non-AKI group ( P &lt;0.001, P &lt;0.001, and P &lt;0.001, respectively). MAKE-free survival in the AKI group was significantly shorter than that in the non-AKI group ( P &lt;0.001). After adjustment for confounding variables, including age, comorbidity, preoperative renal function, and hydronephrosis, AKI was independently and significantly associated with shorter MAKE-free survival (Table). Conclusions: Perioperative AKI had a negative impact on future renal outcomes in patients who underwent RC. Multivariable analysis for MAKE-free survival. Factor P value Hazard ratio 95% CI Age Continuous 0.730 1.005 0.978–1.033 Body mass index Continuous 0.051 1.068 1.000–1.142 Hypertension Presence 0.454 1.182 0.762–1.834 Dyslipidemia Presence 0.187 1.397 0.850–2.296 Diabetes mellitus Presence 0.370 1.257 0.762–2.072 Preoperative eGFR Continuous 0.146 0.990 0.977–1.003 Grade of hydronephrosis Continuous &lt;0.001 1.509 1.206–1.888 Laterality of hydronephrosis Bilateral 0.301 0.734 0.409–1.318 AKI Positive 0.003 1.932 1.254–2.977
A phase 1b/2 study evaluating the activity of tinengotinib in combination with androgen receptor pathway inhibitors (ARPIs) in patients with metastatic castration resistant prostate cancer (mCRPC).
Authors: Wassim Abida, Yu Chen, Deaglan Joseph McHugh, Michael J. Morris, Frank Wu, Peng Peng, Katie Hennessy, Hui Wang, Jean Fan, Samir Zaidi
Journal: Journal of Clinical Oncology (2025)

TPS290 Background: Androgen receptor pathway inhibitors (ARPIs) are standard life-prolonging therapies for patients with metastatic castration-resistant prostate cancer (mCRPC), but patients ultimately progress on these agents. Resistance has been shown to occur in part via lineage plasticity mediated by increased activity of kinases including JAK1 and FGFR. Preclinical studies have shown that ARPI sensitivity can be restored by inhibiting these kinases. Tinengotinib is an orally bioavailable, potent multi-kinase inhibitor that targets JAK1 and receptor tyrosine kinases (FGFRs, VEGFRs). We hypothesize that in patients with mCRPC who are progressing on ARPIs, the addition of tinengotinib will restore sensitivity to ARPIs and result in objective responses. Methods: This is a multi-center, phase 1b/2 study of tinengotinib plus either abiraterone/prednisone or enzalutamide in patients with mCRPC. Eligible patients must be on ongoing therapy with abiraterone/prednisone or enzalutamide started at least 90 days prior to study participation consent and progressing by Prostate Cancer Working Group 3 (PCWG3) criteria. Tinengotinib will be added to abiraterone/prednisone or enzalutamide at the time of progression. Phase 1b (N = up to 24) uses a 3+3 de-escalation schema to assess the safety and tolerability of tinengotinib with either abiraterone/prednisone or enzalutamide. The starting dose of tinengotinib will be 10 mg PO QD, with the possibility of de-escalation to 8 mg PO QD if a combination is not tolerated. Phase 2 employs a two-stage Simon minimax design; patients will be enrolled to evaluate the safety and efficacy of the recommended phase 2 dose (RP2D) of tinengotinib with abiraterone acetate/prednisone or enzalutamide (N = 32). Since abiraterone acetate and enzalutamide target the same pathway, response will be evaluated in combination in the signal-seeking phase 2 portion of the study. As of October 2024, 2 patients have been enrolled in phase 1b across 1 site. Enrollment for phase 2 is expected to begin in January 2025. Clinical trial information: NCT06457919 .
Neoadjuvant darolutamide and relugolix combination preceding radical prostatectomy for high risk localized and locally advanced prostate cancer: A phase I/Ib trial.
Authors: Guru P. Sonpavde, Marcio Moschovas, Carlos A. Alemany, Rajesh Sehgal, Qamar Khan, Justin Emtage, Christopher Russell, Zachary Smith, Steve Williams, John Andrich, Neley Morales, Ritika Behera, Felipe Valerio, Lindley Mosqueda, Jianbin Zhu, Vipul Patel
Journal: Journal of Clinical Oncology (2025)

TPS433 Background: Intensive androgen blockade with combination novel hormonal agent (NHA) + androgen deprivation therapy (ADT) appears promising as neoadjuvant therapy for high-risk localized prostate cancer (PCa) undergoing radical prostatectomy (RP). An all-oral regimen combining relugolix and darolutamide may be feasible, convenient, efficacious and exhibit no significant drug-drug interactions as neoadjuvant therapy for high-risk localized PCa and may convert patients who were initially inoperable to operable. Additionally, the rapid reversibility of castration will allow the reliable determination of post-operative PSA nadir to inform tailored adjuvant therapy. Moreover, given the convenience, this regimen may constitute an excellent backbone to develop additional combinations in future. Hence, a rationale may be made to evaluate the combination of relugolix and darolutamide as neoadjuvant therapy for 12 weeks preceding RP for high-risk localized/locally advanced PCa. Methods: This is a Phase I/Ib non-randomized, uncontrolled, open-label clinical trial evaluating the primary objective of safety and feasibility of combination darolutamide (600 mg PO BID) and relugolix (360 mg on day 1, then 120 mg PO once daily) for 12 weeks as neoadjuvant therapy preceding RP which is to be performed ≥48 hours after and within 2 weeks after completion of neoadjuvant therapy. Patients included in this study must be a candidate for RP with stage cT2-4, N0-1, high risk (defined as Gleason score (GS) ≥ 4 + 3 with ≥ 6 positive systematic biopsies (SB); GS ≥ 4 + 3 with ≥ 3 SB and prostate-specific antigen (PSA) ≥ 20 ng/mL; GS ≥ 9 in ≥ 1 SB or targeted biopsies (TB); or ≥ 2 SB or TB with continuous GS ≥ 8, each with ≥ 80% involvement), histologically or cytologically confirmed adenocarcinoma of the prostate. The Phase I component will accrue 10 patients. If ≥7 patients complete neoadjuvant combination therapy followed by RP with no severe therapy-related adverse events for up to 4 weeks following RP, the regimen is considered feasible and accrual of 20 additional patients continues in the Phase Ib expansion component of the trial to achieve a total of 30 patients. Secondary objectives include clinical response, pathologic complete response with comparison with control matched untreated group that underwent upfront RP, rate of achieving undetectable PSA nadir and testosterone recovery to normal within 8 weeks after RP and post-operative complications. Pharmacokinetic studies are performed in the Phase I component. Blood, tumor and urine are stored for future correlative studies. The trial was activated in October 2024. Clinical trial information: NCT06631521 .
Prospective real world data evaluation of clinical outcomes in metastatic hormone sensitive prostate cancer (MHSPC) patients treated as part of triplet therapy with darolutamide: UK multicenter RECOMMEND study.
Authors: Amit Bahl, Amarnath Challapalli, Prantik Das, Anand Sharma, Rajanee Bhana, Alison Jane Birtle, Dakshinmoorthy Muthukumar, Manreet Randhawa, Santhanam Sundar, Mark Prentice, Diletta Bianchini, Emily Renninson, Miguel CapoMir, Isabel Syndikus, Kamalram Thippu Jayaprakash, Thiraviyam Elumalai, Sarah Goodwin, Omi Parikh, Paul White, Emily Foulstone
Journal: Journal of Clinical Oncology (2025)

89 Background: Darolutamide has authorisation for treatment of metastatic hormone sensitive prostate cancer (MHSPC) in combination with docetaxel chemotherapy and androgen deprivation therapy (triplet therapy) based on ARASENS trial results. The RECOMMEND study is a prospective real-world evaluation (RWE) of clinical outcomes in patients with MHSPC treated with this regimen in the UK. Methods: 318 patients were enrolled from 21 UK centres over 20 months from November 2022. Data cut-off was 14 August 2024. Disease characteristics were evaluated. Descriptive statistics have been used for patient demographics and PSA changes with treatment were analysed. Results: Patients on the study had a median age of 67 (range 38-84) years. Majority of the patients were de novo metastatic (91.2%). 68.2% have a Gleason score ≥8. 76 patients (23.9%) had next generation imaging (NGI) at diagnosis. Performance score was 0 (62.7%) or 1 (37.3%). The distribution of metastases (%) were: bone (84.9), nodal (60.4), lung (12.6) and liver (2.5). The median PSA level was 134 (range 1 to 5628) ng/mL at diagnosis. At the end of docetaxel chemotherapy median PSA was 0.35 ng/mL. PSA response see in the 226 patients who had completed 6 cycles of docetaxel chemotherapy at the data cut-off, PSA 50 was seen in 87.6% (198/226) and PSA 90 in 53.2%. PSA responses in those who only completed 4/5 cycles of docetaxel (n=14) did not significantly differ compared to those who completed all 6 cycles (PSA 50 p=0.445 and PSA 90 p-0.664). At 6 months from darolutamide initiation, quality of life (QoL) data is currently available for 173 patients, of these 88.4% reported either stable or improved QoL and 11.6% had a decline in QoL at the end of chemotherapy. Conclusions: The tolerability and efficacy profile of treatment with ADT+Darolutamide+Docetaxel in MHSPC in the RECOmMEnD study is similar to that reported in the ARASENS trial. The QoL data available for 173 patients to date reports either stable or improved QoL at 6 months for 88.4% cases. This provides important prospective RWE data, enabling patients and clinical teams to make informed choices in this setting.
A retrospective real-world study of disitamab vedotin combined with tislelizumab versus chemotherapy in patients with previously untreated metastatic urothelial carcinoma.
Authors: Han Se, Xiaomeng Gui, Lin Wang, Jing Jing, Riguleng Si, Haojing Li, Dongchen Lv, Jia Li, Ning Chi, Sanxiang Li, Hong Yang
Journal: Journal of Clinical Oncology (2025)

733 Background: Eligible patients with metastatic urothelial carcinoma (mUC) typically receive platinum-based chemotherapy as first-line therapy. Recently, antibody-drug conjugates (ADCs) combined with PD-1 antibody have shown good efficacy and safety in metastatic urothelial carcinoma (mUC). And HER2-positive thought to be an unfavorable prognostic factor and associated with poor outcomes but can benefit from anti-HER2 ADCs such as Disitamab Vedotin (RC48-ADC). The aim of this retrospective study is to evaluate the efficacy and safety of RC48-based therapy in real-world untreated mUC, especially in comparison to standard chemotherapy. Methods: We retrospectively collected data from 70 consecutive patients with mUC who received routine care between July 2022 and December 2023 including 30 received RC48-ADC plus Tislelizumab (DT-group) and 40 received the conventional regimen of Gemcitabine plus Cisplatin (GC-group). Last follow-up on 30 March 2024. The primary endpoints were objective response rate (ORR), disease control rate (DCR), median progression-free survival (PFS), overall survival (OS), and treatment-related adverse events (TRAEs). Results: The median age of the DT-group and GC-group patients were 67-y and 64-y, with 66.7% (n=20) and 82.5% (n=33) HER-2 negative (identified as IHC 0 or 1+). Baseline characteristics of the two groups, including age, gender, pathological grading, ECOG score, tumour location, metastasis and HER-2 expression showed no statistically difference (P &gt; 0.05). The ORR in DT-group was 1.5 times higher than in GC-group, reaching 73.3% (22/30) versus 47.5% (19/40) with a higher CR rate (20% vs 0%). Even in HER-2 negative subgroup from DT-group, the RC48-ADC plus Tislelizumab therapy achieved impressive outcomes (ORR 55% (11/20)) comparable to chemotherapy. For survival analyses, PFS was longer in the DT-group than in GC-group (median, 10.98 months vs. 7.67 months; P&lt;0.005), as was OS (median, not reached vs. 11.34 months). Two groups showed a similar safety profile (p &gt; 0.05). The most reported TRAEs were bone marrow suppression, gastrointestinal and hepatobiliary disorders, malaise, alopecia and rash, and no ≥ grade 3 TRAEs or treatment-related deaths were reported. Conclusions: This retrospective study of patients with treatment-naïve mUC demonstrated administration of RC48 for real-world patients is both effective and safe. Several global clinical trials (DV-001, RC48-G001) evaluating efficacy and safety of RC48-ADC in combination with immunotherapy are ongoing. These data further solidify the benefit of anti-HER2 ADC combined with checkpoint inhibitors for frontline treatment of patients with mUC.
Detection of mutations in homologous recombination repair (HRR) pathway genes using liquid biopsy in metastatic, castration-resistant prostate cancer (mCRPC) patients without tumor tissue availability.
Authors: Yoojoo Lim, Dong Soo Kyung, Won Yeong Ko, Hwang-Phill Kim, Tae-You Kim
Journal: Journal of Clinical Oncology (2025)

98 Background: Accurate detection of mutations in HRR pathway genes among patients with mCRPC is essential for selecting patients who would benefit with poly (ADP-ribsose) polymerase (PARP) inhibitor therapies. Traditional tissue-based detection methods can be associated with practical challenges as acquisition of specimens can involve significant risk or high costs. For prostate cancer patients, obtaining adequate tissue samples can be even more difficult, considering the unique characteristics of the disease. This study aimed to evaluate the real-world performance of liquid biopsy using circulating tumor DNA (ctDNA) in detecting mutations in HRR genes, among mCRPC patients who did not have tissue available for genomic evaluation. Methods: Blood samples (20ml of whole blood) were collected from 760 mCRPC patients in 10 Asian countries. Samples were collected once for each patient, regardless of treatment type or cycles as long as the patients were followed up for their mCRPC. All patients included were confirmed from each participating site to have no tissue available for genomic analysis. Blood samples were analyzed using a next-generation sequencing (NGS) based ctDNA assay, covering 15 genes in the HRR pathway ( ATM, BARD1, BRCA1, BRCA2, BRIP1, CDK12, CHEK1, CHEK2, FANCL, PALB2, PPP2R2A, RAD51B, RAD51C, RAD51D, RAD54L) . Results: ctDNA NGS testing was successfully performed in all 760 mCRPC patients. Any mutations in the HRR pathway genes were detected in 63.7% of the included patients and deleterious or suspected deleterious HRR pathway gene mutations were detected in 32.5% with the assay. Deleterious/suspected deleterious BRCA1/2 mutations were detected in 68/760 (8.95%) of the cases. Other detected deleterious/suspicious deleterious mutations included mutations in CDK12 , detected in 59/760 (7.76%) patients, followed by ATM mutation in 39/760 (5.13%), and CHEK2 in 31/769 (4.08%) by frequency. Conclusions: ctDNA testing for HRR gene mutations offers a practical tool for therapy selection in mCRPC patients. This non-invasive approach enables testing for patients who were not eligible for evaluation by tissue-based methods and can expand access to adequate targeted therapies.
Avelumab first-line (1L) maintenance therapy in advanced urothelial carcinoma: Final analysis from a real-world study in the UK.
Authors: Robert Jones Jones, Yatri Shah, Alison Jane Birtle, Amarnath Challapalli, Joachim Chan, Deborah Enting, Andrew Hudson, Mark David Linch, Sophie Otter, Andrew Protheroe, Anand Sharma, Rufus Turner, Bhagyalakshmi Chengat Prakashbabu, Wendy Rice, Elima Enaji Jedy-Agba
Journal: Journal of Clinical Oncology (2025)

723 Background: In the JAVELIN Bladder 100 phase 3 trial, avelumab 1L maintenance therapy plus best supportive care (BSC) significantly improved overall survival (OS) and progression-free survival (PFS) vs BSC alone in patients with locally advanced or metastatic urothelial carcinoma (la/mUC) that had not progressed with 1L platinum-based chemotherapy (PBC). In the UK, initial access to avelumab was provided via the Early Access to Medicines Scheme (EAMS) from September 2020. This study reports 24-month real-world outcomes in patients treated with avelumab 1L maintenance via the EAMS in the UK. Methods: Patients aged ≥18 years who had been diagnosed with la/mUC, demonstrated at least stable disease following 1L PBC, and initiated avelumab since October 2020 were recruited consecutively from 10 UK hospitals. Primary outcomes included real-world OS, real-world PFS, and treatment patterns by 24 months. Recruitment was completed in June 2022, and all patients had completed 24 months of follow-up from avelumab initiation by June 2024. Results: Of 106 patients recruited, 78 (73.6%) were male. Median age at diagnosis of la/mUC was 72 years. Primary tumor site was bladder in 40 (78%), and the most common metastatic sites were lymph node in 64 (60.4%), lung in 31 (33%), and bone in 20 (21.3%). ECOG performance status was 0 in 35 (33.0%),1 in 36 (34%), 2-4 in 5 (4.7%), and not recorded in 30 (28.3%). 1L PBC was carboplatin/gemcitabine in 55 (51.9%) and cisplatin/gemcitabine in 49 (46.2%). Response to 1L PBC was partial or complete response in 63 (60.0%). From avelumab initiation, median OS was 16.8 months (95% CI, 11.6-23.4) and median PFS was 8.7 months (95% CI, 7.1-14.2). Median OS from the start of 1L PBC in this population without disease progression after 1L PBC was 21.8 months (95% CI, 17.0-28.9). In subgroup analyses of patients who had received 1L carboplatin/gemcitabine or cisplatin/gemcitabine, median OS from avelumab initiation was 14.4 months (95% CI, 10.1-not estimable [NE]) and 21.4 months (95% CI, 15.4-NE), and median OS from start of 1L PBC was 19.5 months (95% CI, 14.8-NE) and 26.7 months (95% CI, 20.5-NE), respectively. Conclusions: These results provide evidence of the clinical effectiveness of avelumab 1L maintenance therapy in patients who were progression free following 1L PBC in a UK real-world setting. Median OS was shorter than previously observed in the JAVELIN Bladder 100 trial, which may be due to the worse ECOG performance status and higher proportion of patients who had received 1L carboplatin-based chemotherapy in this real-world population.