tbuckley/cabot-search huggingface dataset:
Mevrometostat (PF-06821497) in combination with enzalutamide in patients with metastatic castration-resistant prostate cancer previously treated with abiraterone acetate: The phase 3, randomized MEVPRO-1 study.
Authors: Neeraj Agarwal, Michael Thomas Schweizer, Elena Castro, Arun Azad, Daniel J. George, Jayeta Chakrabarti, Sujata Narayanan, Yiyun Tang, Karim Fizazi
Journal: Journal of Clinical Oncology (2025)

TPS288 Background: Resistance to androgen receptor (AR) pathway inhibitors (ARPI; e.g., abiraterone, enzalutamide) in metastatic castration-resistant prostate cancer (mCRPC) may be driven by preservation of AR signaling through various mechanisms. Enhancer of zeste homolog 2 (EZH2) is implicated in the pathogenesis of prostate cancer and ARPI resistance. Combining ARPI with therapies that modulate alternative signaling pathways, including epigenetic modifiers such as EZH2, could be a promising treatment approach to overcome resistance. Mevrometostat (PF-06821497) is a potent and selective small molecule EZH2 inhibitor. Results from the dose-escalation period of a phase 1 study (NCT03460977) showed promising activity for mevrometostat combined with enzalutamide, with a manageable adverse-event profile in abiraterone-exposed patients with mCRPC (Schweizer MT, et al. J Clin Oncol . 2024;42(16_suppl):5061). The current trial aims to evaluate radiographic progression-free survival (rPFS), overall survival (OS), and safety of mevrometostat plus enzalutamide compared with standard of care in patients with mCRPC previously treated with abiraterone. Methods: MEVPRO-1 (NCT06551324) is a global, open-label, phase 3 trial in patients with mCRPC aged ≥18 years with progression on/after ≥12 weeks abiraterone, castration testosterone levels ≤50 ng/dL, ECOG performance status 0–2, and life expectancy ≥6 months. Approximately 600 patients will be randomized 1:1 to receive mevrometostat (875mg BD with food) with enzalutamide (160mg QD), or physician’s choice of enzalutamide (160mg QD) or docetaxel (75mg/m 2 intravenously every 21d). Randomization will be stratified by previous docetaxel in metastatic castration-sensitive setting, physician’s choice of comparator (enzalutamide/docetaxel), and presence of hepatic metastases. The primary endpoint is BICR-assessed rPFS per RECIST 1.1 (soft tissue) and PCWG3 (bone) assessed by blinded central radiology review. Key secondary endpoint is OS. Secondary endpoints include anti-tumor activity, safety, pharmacokinetics, ctDNA, and patient-reported outcomes. Stratified log-rank P -values, HRs, and 95% CIs will be estimated using a stratified Cox proportional hazard model, and Kaplan–Meier analysis will summarize time-to-event endpoints. Clinical trial information: NCT06551324 .
A prospective, single-center, single-arm clinical study of adjuvant toripalimab combined with axitinib in non-clear renal cell carcinoma (nccRCC) patients with high-risk recurrence factors (IUNU-RC-102).
Authors: Guangxiang Liu, Shun Zhang, Haixiang Qin, Changwei Ji, Hongqian Guo
Journal: Journal of Clinical Oncology (2025)

TPS613 Background: Non-clear cell renal cell carcinoma (nccRCC) accounts for approximately 25–30% of all renal cell carcinoma (RCC) cases and is associated with a poor prognosis. While early-stage treatment typically involves surgery, there is a significant risk of postoperative recurrence. Once recurrence or distant metastasis occurs, management becomes more challenging. Current clinical trial results for metastatic advanced nccRCC have shown variability, and no standard treatment protocol has been established. For advanced clear cell renal cell carcinoma (ccRCC), however, the combination of immunotherapy and targeted therapy has become the standard of care. The RENOTORCH study demonstrated the efficacy and safety of toripalimab combined with axitinib as a first-line treatment for advanced ccRCC[1]. This study aims to investigate the efficacy and safety of toripalimab combined with axitinib as adjuvant therapy in postoperative patients with high-risk nccRCC. Methods: IUNU-RC-102 (NCT05768464) is a single-center, prospective, single-arm clinical trial. The study plans to enroll 30 patients. Key inclusion criteria include: a clinical diagnosis of high-risk recurrent nccRCC following nephrectomy, age between 18 and 75 years, an ECOG performance status of 0–1, no prior systemic therapy for renal cancer, and confirmed pathological histology of nccRCC following partial or radical nephrectomy, with exclusions for clear cell carcinoma, chromophobe carcinoma, and eosinophilic renal cell carcinoma. All participants will receive axitinib (5 mg twice daily) for 4 weeks, along with toripalimab (240 mg intravenously on the first day of each 21-day cycle). The treatment duration will extend up to 52 cycles. The study follows Simon’s minimax two-stage design. In the first stage, three patients will be enrolled and will receive two treatment cycles to assess safety. If dose-limiting toxicity (DLT) occurs in one or more of the three patients, the study will be paused. Investigators will then determine whether to terminate or amend the study protocol after further deliberation. In the second stage, the primary endpoint will be 2-year disease-free survival (DFS). Secondary endpoints will include 3-year overall survival (OS), disease recurrence-specific survival (DRSS), and safety. The first participant was enrolled in IUNU-RC-102 in October 2023. We anticipate that the combination of toripalimab and axitinib will offer a promising new treatment option for these patients. Clinical trial information: NCT05768464 .
Management of relapsed primary retroperitoneal (RP) germ-cell tumor (GCT) after front-line chemotherapy.
Authors: Kirsten Lewis, Rebecca Hassoun, Sandra K. Althouse, Tareq Salous, Nasser H. Hanna, Lawrence H. Einhorn, Nabil Adra, Jennifer King
Journal: Journal of Clinical Oncology (2025)

637 Background: Primary RP GCT represents a rare subset of extragonadal GCTs. While front-line therapy remains similar to gonadal GCT, there is limited data on management of relapsed disease for these patients (pts). Here, we describe management and outcomes of pts with relapsed primary RP GCT. Methods: The prospectively maintained Indiana University testicular cancer database was queried for patients with primary RP GCT who relapsed after first-line therapy between 1990-2024. Kaplan-Meier method was used to analyze progression free survival (PFS) and overall survival (OS). Survival outcomes based on type of second-line chemotherapy was compared using the log rank test. Results: 53 pts were included in the analysis. Median age at diagnosis was 33.7yrs (17.4-67.9). Primary tumor pathology was non-seminoma in 75.5% and seminoma in 24.5%. Predominant histology was seminoma (30.2%), mixed (26.4%), choriocarcinoma (17.0%), yolk sac tumor (13.2%), embryonal (9.4%), teratoma (3.8%). Other metastasis sites included pulmonary (56.6%), liver (35.9%), posterior mediastinum (15.1%), pelvic lymph nodes (13.2%), brain (13.2%), bone (9.4%). IGCCCG risk was good in 30.2%, intermediate in 15.1%, and poor in 54.7%. First-line chemo was BEPx4 (54.6%), VIPx4 (11.3%), BEP x3 (7.5%), EPx4 (7.6%), BEPx2 + HDCTx2 (2.0%), and other (17.0%). All 53 pts had progression of disease after first-line chemo. 44 received salvage chemotherapy, 5 received RPLND, 2 other salvage surgery, 1 radiation, and 2 received no salvage therapy. Salvage chemo was HDCT for 69.8% vs. standard salvage chemo for 30.2%. For pts treated with HDCT, 83% completed 2 cycles. 46.7% of those treated with HDCT progressed afterward. Of pts who had salvage RPLND, 3 were found to have teratoma and 2 had active GCT. 2 pts had other salvage surgery; 1 had thoracotomy with GCT and 1 had craniotomy with GCT. At time of last follow-up, 28.3% of all pts were alive with NED, 11.3% were alive with disease, 13.2% were lost to follow-up, and 47.2% had died of disease. The table lists PFS and OS by salvage chemo type. Conclusions: Patients with relapsed primary RP GCT seem to have worse outcomes compared with historical results from relapsed gonadal GCT. A subset of patients with relapsed primary RP GCT are curable with salvage therapy. Survival outcomes by salvage chemotherapy received. HDCT N=30 Standard dose chemo N= 14 p-value 2-yr PFS 47.7% (95% 28.7-64.5) 31.8% (95% 7.7-59.9) p=0.18 2yr OS 53.8% (95% 34.0-70.0) 68.6 (95% 30.5-88.7) p=0.84
Efficacy of selective renal tumor embolization combined with axitinib and reduced-dose toripalimab in oligometastatic clear cell renal carcinoma: A comparative analysis with axitinib combined with standard-dose toripalimab.
Authors: Jun Du, Feiran Chen, Chao Zhang, Jie Tian, Li Zhang, Qing Yang, Xin Yao
Journal: Journal of Clinical Oncology (2025)

532 Background: Oligometastatic renal cell carcinoma (RCC) involves limited metastases (1-5) and lies between localized and metastatic disease, with lower tumor burden. Studies suggest these patients may respond well to local or systemic therapies like targeted or immunotherapy. Combining renal tumor embolization with these therapies is emerging as a promising option. However, comparative data on embolization versus non-embolization treatments remain scarce. This study compares efficacy and adverse events of these treatments in oligometastatic RCC using propensity score matching. Methods: This study included oligometastatic clear cell RCC patients treated since March 2023, divided into two groups. The experimental group received renal tumor embolization, axitinib (5 mg twice daily), and reduced-dose toripalimab (160 mg every 3 weeks). The control group received standard axitinib and toripalimab (240 mg every 3 weeks). All patients had their first follow-up three months post-treatment to assess efficacy and adverse effects. Propensity score matching (PSM) was used to balance demographics, tumor characteristics, and treatment history. The primary outcomes were disease control rate (DCR) and partial response rate (PR), with secondary outcomes being grade 3-4 adverse events. Results: 58 patients were included, 29 in each group after matching. All covariates had SMD values &lt; 0.1, indicating good baseline balance. The experimental group had a DCR of 100% and PR of 93.1%, compared to DCR of 69.8% and PR of 56.7% in the control group (P &lt; 0.05). In 4 patients with renal vein tumor thrombus, tumor size reduced by over 50%, and thrombus control was effective. Grade 3-4 adverse events were lower in the experimental group (10.1% vs. 38.4%, P &lt; 0.05), mainly hypertension, hand-foot syndrome, and liver dysfunction. Conclusions: Propensity score matching showed that renal tumor embolization combined with axitinib and reduced-dose toripalimab improved efficacy and reduced grade 3-4 adverse events in oligometastatic RCC patients. Larger randomized trials are needed to confirm these findings and explore personalized treatment strategies to improve long-term survival and quality of life.
Examining community social vulnerability domains and influence on treatment selection for men with prostate cancer.
Authors: Jason Lloyd Goodloe, Samuel L Washington, Lufan Wang, Janet E Cowan, Hao Nguyen, Peter Carroll, June M. Chan, Salma Shariff-Marco
Journal: Journal of Clinical Oncology (2025)

363 Background: For men with clinically localized PCa, treatment selection guided by patient age, comorbidities, and tumor characteristics can offer improved outcomes. While informative, these observations remain difficult to translate into local, state, and federal policy change to eliminate health disparities for communities at greater risk. We sought to examine how community SVI influences primary treatment, a key determinant of cancer outcomes, for men with clinically localized PCa treated primarily in a community setting. Methods: Men diagnosed and managed in CaPSURE practices after 1998 with clinically localized disease (no cM+ or cT4) and who underwent primary management within six months of diagnosis were identified. Community social vulnerability, as defined by census tract-level rankings from 0 to 1 with &gt;90 th percentile deemed high, was appended to participants’ geocoded baseline addresses. SVI encompasses four domains (socioeconomic status, household characteristics, racial and ethnic minority status, and housing type and transportation). Prostate cancer treatment included prostatectomy, radiation, active surveillance/watchful waiting (AS/WW), primary androgen deprivation therapy (pADT). Multivariate multinomial logistic regression analyses examined associations between SVI and treatment selection, adjusted for patient, clinical, and tumor characteristics with sensitivity analyses using each SVI domain. Odds ratios and confidence intervals were reported with a two-sided p-value &lt; 0.05 considered significant. Analysis was performed with SAS 9.4 for Windows. Results: 9,023 men diagnosed with low (43%) or intermediate (42%) risk disease and treated at community urology practices (90%) were included. Half (52%) underwent prostatectomy, 26% radiation, 13% ADT, and 9% AS/WW. Median SVI was 0.37 (IQR 0.17-0.59) and varied by theme: socioeconomic status (median 0.35, IQR 0.18-0.57), household characteristics (median 0.41, IQR 0.22-0.64), racial and ethnic minority status (median 0.37, IQR 0.17-0.63), and housing type and transportation (median 0.44, IQR 0.21-0.70). Correlations between SVI themes varied broadly (r = 0.21-0.63, p &lt; 0.001). Having high SVI was associated with increased odds of non-invasive treatment compared to RP: RT (OR 1.56, 95% CI 1.39-1.77), AS/WW (OR 1.21, 95% CI 1.0-1.45), or pADT (OR 1.51, 95% CI 1.27-1.79). Individuals with high SVI by household characteristics had significantly greater likelihood of pADT (OR 1.61, 95% 1.34-1.94) compared to RP. Conclusions: Community social vulnerability independently increases the likelihood of non-surgical and potentially non-curative management of prostate cancer. SVI domains can provide specificity into which community characteristics may drive vulnerability and aid in identifying communities for targeted, policy-focused interventions.
Adherence to Antihypertensive Medications and Determinants Among Patients at Yekatit 12 Hospital, 2022 G.C.
Authors: Kidist Kenea Madessa
Journal: Clinical Cardiology and Cardiovascular Interventions (2025)

Background: Hypertension is a major global issue, with high morbidity and mortality rates. It is estimated to be 6% in Ethiopia and 30% in Addis Ababa. Adherence is the degree to which a person's medication-taking behaviour corresponds to the health care provider's medical advice. It encompasses both dosage frequency and timing of ingestion. Poor adherence is connected with poor illness outcomes and a waste of healthcare expenditures. Objective: To assess the extent of Adherence to antihypertensive medications and the reasons for non-adherence among hypertensive patients. Methodology: An institution-based cross-sectional study was conducted at Yekatit12 Hospital Medical College using structured questionnaires from February to May 2022 G.C. The collected data was processed and analyzed using computer software using SPSS version 21.0, presented in tables and figures and then interpreted based on the findings. Results: - Of 127 respondents, 78 (61.9%) and 49 (38.8%) were Female and Male, respectively. The majority of the study participants, 73 (57.6%), were in the age group of 50-64. In a more significant proportion of patients, 88(69.4%), the cost of drugs was covered by themselves. At least one side effect of hypertensive medications had been reported by 60 (80%) of participants. Of the 127 study subjects, 79 (62.2%) were adherent, (37.8%) were non-adherent to their antihypertensive medication. The majority of patients (41.2%) reported stopping their medication when they felt better &amp; only (10.2%) of them reported financial problems with stopping their medication. Conclusion and Recommendation: - In general, these hypertensive individuals did not take their medications as prescribed. To enhance the patient's quality of life, pharmacists and other medical specialists must to work together. They must emphasize the value of following their hypertension treatment plan, its advantages, and the possibility of problems.
Clinical significance of urotensin 2 plasma level in patients diagnosed with prostate cancer.
Authors: Cigdem Dinckal, Zeynep Gulsum Guc, Huriye Erbak Yilmaz, Mustafa Dinckal, Semiha Ozgul, Gamze Ozkan, Sinan Unal, Yasar Yildiz, Utku Oflazoglu, Tarik Salman, Ahmet Alacacioglu, Yuksel Kucukzeybek
Journal: Journal of Clinical Oncology (2025)

249 Background: Urotensin-II is a small somatostatin-like cyclic peptide characterized by its potent vasoconstrictor activity. Urotensin-II (UT-II) and its receptor (UTR) have been shown to play a role in the formation of different epithelial cancers. To date, many studies have been reported in prostate cancer that provide genetic contributions with diagnostic, prognostic and therapeutic potential for carcinogenesis. However, the role of urotensin-II in prostate carcinogenesis has not yet been elucidated. There are several limitations to using PSA as a biomarker in prostate cancer follow-up. More accurate and specific biomarkers are needed to improve diagnosis and monitoring of prostate cancer. Our study aimed to reveal the clinical importance of plasma UT-2 level in metastatic prostate cancer patients and to investigate its correlation and prognostic importance with clinical parameters such as PSA level and pathological parameters such as Gleason Score. Methods: Patients who applied to İzmir Katip Celebi University Atatürk Training and Research Hospital Medical Oncology Polyclinic in 2023 were included in our study. The demographic information of the patients was scanned from the oncology file system and recorded. Measurements of plasma ÜT-2 level were made by a biochemistry specialist at İzmir Katip Celebi University Atatürk Training and Research Hospital Biochemistry Laboratory. For the ELISA method, Urotensin 2 ELISA (Elabscience lot no: E-EL-2047) kit was used in the Biotek (ELx800, USA) semi-automatic ELISA device. Results: A total of 147 patients, 100 metastatic and 47 control groups, were included in our study. No statistically significant difference was observed between the groups in terms of additional diseases that may be related to UT-2 level: Diabetes Mellitus, hypertension, peripheral artery disease, coronary artery disease, chronic renal failure and smoking characteristics (p&gt;0.05). When the PT-2 level was compared between the de-novo and non-de-novo metastasis groups and the control groups, both metastasis groups had a higher average than the control groups (p = 0.004). The cut-off value for UT-2 was determined as 1.269 ng/mL. UT-2 sensitivity, specificity, positive predictive value and negative predictive value were found to be 81%, 53%, 79% and 57%, respectively. Conclusions: Today, studies are continuing rapidly to increase the efficiency of PSA and to find new tumor markers. In our study, UT-2 levels in metastatic prostate cancer patients were found to be statistically higher than other groups. This is the first study in the literature to study the UT-2 plasma level in prostate cancer, and UT-2 may be an important biomarker in predicting prognosis in prostate cancer.
Bipolar androgen therapy (BAT) for nonmetastatic castration-resistant prostate (nmCRPC) cancer progressing on darolutamide: Working Out M0 BAT (WOMBAT; ANZUP 2201).
Authors: Megan Crumbaker, Laurence Krieger, David William Pook, Ian D. Davis, Antoinette Fontela, Christopher Oldmeadow, Josh Hurwitz, Andrisha Jade Inderjeeth, Haryana M. Dhillon, Teesha Downton, Gavin M. Marx, Samantha Shekar, Emmanuel S. Antonarakis, Samuel R. Denmeade, Angelyn Anton, Thean Hsiang Tan, Sharad Sharma, Jeffrey C. Goh, Lisa Horvath, Anthony M. Joshua
Journal: Journal of Clinical Oncology (2025)

TPS298 Background: The backbone of prostate cancer systemic treatment is androgen deprivation therapy (ADT) increasingly with the use of androgen receptor pathway inhibitors (ARPIs). Mechanisms for ARPI resistance include amplification of the androgen receptor (AR), overexpression of AR variants, aberrant AR activity, and autocrine/paracrine androgen synthesis in tumour cells. Preclinical and clinical studies have identified that bipolar androgen therapy (BAT) may restore the sensitivity of prostate cancer to ARPIs. We plan to test this hypothesis in patients with PSA progression on darolutamide for non-metastatic castrate resistant prostate cancer. Methods: WOMBAT (ANZUP 2201, NCT06594926, ACTRN12624000582550) is a single-arm phase 2 trial. The primary endpoint is to determine metastasis-free survival (MFS; time from commencing BAT to evidence of metastases or death, by conventional imaging as per PCWG3 criteria). Secondary endpoints include toxicity of BAT and darolutamide; effects on health-related quality of life; efficacy measures (PSA response rate; PSA progression-free survival); effects of BAT and darolutamide on bone turnover. Inclusion criteria include: PSA progression on darolutamide for nmCRPC; M0 on conventional imaging. Treatment consists of BAT (IM testosterone enanthate 500mg) day 1 and darolutamide 600mg bd days 29-56 (of a 56-day cycle) with ongoing ADT. The total sample size of 69 (with a first stage of enrolment of 44) is calculated to demonstrate an increase in the proportion of participants without detectable metastases at 6 months from 56.1% to 66.7% (corresponding to a median MFS improvement from 7.2 to 10.27 months, HR 0.6) with a one-sided type I error of α = 10% and power of 80%, based on benchmarks from the ARAMIS trial of darolutamide in nmCRPC. Enrolment has commenced at 8 sites around Australia. Clinical trial information: ACTRN12624000582550 .
Cabozantinib in patients (pts) with non-locally pretreated brain metastases (BM) from renal cell carcinoma (RCC): Results of the multicenter CABRAMET phase II trial (NCT03967522).
Authors: Sylvie Negrier, Loic Mourey, Ellen Blanc, Marine Gross-Goupil, Aude Flechon, Ronan Flippot, Philippe Barthelemy, Stephane Oudard, Emeline Colomba, Constance Thibault, Alain Ravaud, Christine Chevreau, Mathilde Donnat, Helen Jane Boyle, Cécile Dalban, David Pérol, Bernard Escudier, Laurence Albiges
Journal: Journal of Clinical Oncology (2025)

533 Background: Despite dramatic progress in metastatic RCC treatments, pts with BM remain with poor outcome and were mostly excluded from clinical trials. Local treatments on BM are standard today. Methods: Adult pts with histologically proven RCC and BM ≥ 5 mm (or &gt; 8 mm if solitary) including at least one non-locally pretreated, &lt; 3 prior systemic treatments excluding cabozantinib, ECOG PS 0 or 1 and steroids &lt; 40 mg/day were included. Primary endpoint was BM progression free survival rate at 6 months (6m-BM-PFS) according to modified RANO-BM criteria by central review. Secondary endpoints were BM response and response duration, extracranial response, PFS, overall survival and safety. 25 evaluable pts were required to evaluate the main endpoint. Results: 26 pts were included, 25 were evaluable for the primary endpoint and median follow up time was 39.8 months [5.9-49.7]. The 6m-BM-PFS was 56.0% [unilateral 95%CI 37.9-] (14/25 pts). BM response was partial response (PR) for 61.5% (16/26) pts and median duration of response was not reached, 66.7% pts being event-free 24 months after BM response. Extracranial response was PR for 38.5% (10/26). Median PFS was 8.1 months [95%CI 4-11.9], and median BM PFS 8.4 months [95%CI 5.4-NR]. Median overall survival was 15.8 months [95%CI 9.7-35.0]. No new safety signals were observed. Conclusions: This is the first prospective trial assessing cabozantinib in RCC pts with non-locally pretreated BM. These results confirm the efficacy of cabozantinib on BM previously reported in retrospective series. Clinical trial information: NCT03967522 . Pts characteristics. Pts number N = 26 Median age (years) [range] 67 [44-86] Gender: F / M, n 5 / 21 ECOG PS: 0 / 1,n 10 / 16 RCC: non-clear cell / clear cell, n 2 / 24 Prior nephrectomy : n 16 Number of BM: 1 / 2 / &gt;3, n 9 / 7 / 10 Prior BM treatments: Overall/ Surgery/ Radiation, n 10 / 3 / 10 Prior systemic treatment: 0 / 1 / &gt;2, n 7 / 15 / 4 IMDC: Favorable / Intermediate / Poor, n 7 / 10 / 9