tbuckley/cabot-search huggingface dataset:
Management of relapsed stage I seminomatous germ cell tumor with retroperitoneal or pelvic only relapse.
Authors: Ahmed Bilal Khalid, Sandra K. Althouse, Rebecca Hassoun, Tareq Salous, Clint Cary, Timothy A. Masterson, Lawrence H. Einhorn, Nabil Adra, Jennifer King
Journal: Journal of Clinical Oncology (2025)

630 Background: For patients (pts) with stage 1 seminomatous germ cell tumor (SGCT) on active surveillance (AS), front-line therapy depends on the location and extent of relapse. We describe the characteristics and management of pts on AS with stage I SGCT with relapse in the retroperitoneum (RP) or pelvis only. Methods: The prospectively maintained Indiana University testicular cancer database was queried for pts with stage 1 SGCT on AS w/ RP or pelvic only relapse between 1990-2024. Pts were categorized into a chemotherapy, surgery, or radiation (XRT) group based on treatment at relapse. Comparisons between groups were done using Chi-square tests for categorical variables or Kuskal-Wallis test for continuous variables. Kaplan-Meier method was used to analyze progression-free survival (PFS) and overall survival (OS) using the log rank test to compare groups. Results: We identified 71 pts with stage 1 SGCT on AS w/ relapse in the RP or pelvis only. The median age at diagnosis was 37.2 yrs (range, 19.5-74.5). IGCCCG risk was good in all pts. At time of relapse, 37 pts (52.1%) were treated with chemo, 20 with surgery (28.2%), and 14 (19.7%) with XRT. The median time to relapse on stage I AS for pts treated with chemo was 9.5 months (0.84-91.7) compared to 19.9 months (1.6-60.2) with surgery and 13.1 months (4.6-48.8) with XRT (p=0.13). Chemo regimens used were BEP X 3 (62.2%), EP X 4 (21.6%), BEP X 4 (2.7%) and other (13.5%). 68 pts (95.8%) relapsed in the RP; 3 (4.2%) relapsed in the pelvis only. All 9 pts with lymph node (LN) size &gt;5 cm were treated with chemo. In the 32 pts with LN size &lt;3 cm, 12 (37.5%) were treated with surgery, 12 (37.5%) with chemo, and 8 (25%) with XRT. 11 total pts (15.5%) relapsed after front-line therapy and thus required multimodality treatment. This included 8 (21.6%) in the chemo group who relapsed; 2 out of 8 required RPLND while 6 were treated with salvage or high dose chemotherapy. 1 patient (5%) in the surgery group relapsed and required chemotherapy. In the XRT group, 2 pts (14.3%) relapsed; 1 was treated with salvage chemo and 1 with surgery. With a median follow-up time of 3.03 yrs (0-14.8), the 2-yr PFS for pts treated with chemo was 73.8%, surgery was 95%, and XRT was 92.3% (p=0.14). 2-yr OS was 100% for all treatment groups (p=0.58). Conclusions: In pts on AS with stage I SGCT w/ RP or pelvic only relapse, there was no difference in survival outcomes based on front-line therapy received. In this cohort of pts carefully selected for RPLND, the majority were cured with single-modality therapy; most of these pts had RP lymph nodes &lt;3cm with a longer median time to relapse while on AS.
NSD2 inhibition as a therapeutic approach for treatment-induced neuroendocrine prostate cancer.
Authors: Lan Xu, J Erin Flynt, Sanjana Miskin, Luis Miguel Mendes Soares, Eva Corey, Terry Connolly, Benjamin Winograd
Journal: Journal of Clinical Oncology (2025)

198 Background: Trans-differentiation from adenocarcinoma to neuroendocrine histology is a major treatment-induced resistance mechanism against androgen receptor pathway inhibitors (ARPI) in castration-resistant prostate cancer (CRPC). With increased use of ARPI in the clinic, neuroendocrine prostate cancer (NEPC) constitutes 15~20% of CRPC. The histone H3 K36 di-methyltransferase NSD2 has recently been shown to be a driver of the adeno-to-neuroendocrine trans-differentiation. The level of NSD2 expression is markedly increased in AR(-) NEPC compared to AR(+) CRPC and correlates with a poor disease outcome. Furthermore, genetic depletion of NSD2 has been shown to reverse AR(-) NEPC to an AR(+) adenocarcinoma phenotype and re-sensitize the prostate cancer cells to enzalutamide treatment. Methods: K36 Therapeutics has developed a selective NSD2 inhibitor KTX1001 that is currently undergoing clinical evaluation in multiple myeloma (NCT05651932). Dose proportional pharmacokinetics and on-target pharmacodynamics of KTX1001 have been observed as well as an excellent safety profile in patients. Here we have investigated whether pharmacological inhibition of NSD2 reverses AR(-) NEPC to AR(+) adenocarcinoma in preclinical models. Results: In the NEPC cell line NCI-H660, KTX1001 treatment led to a significant change in the epigenome landscape, resulting in reduced expression of neuroendocrine markers SYP, CHGA and FOXA2 and concomitant upregulation of the adenocarcinoma markers AR, NKX3.1 and KLK3. These observations are consistent with a lineage change from AR(-) NEPC to AR(+) adenocarcinoma. We further investigate this in vivo using a NEPC patient-derived xenograft model. Indeed, treatment with our selective NSD2 inhibitor resulted in pronounced upregulation of the Hallmark Androgen Response gene signature, suggesting restoration of the AR-signaling pathway. Moreover, Hallmark E2F and Myc signatures, which are known to be elevated in NEPC cells, were markedly downregulated after NSD2 inhibitor treatment. These observations suggest a significant change in NEPC lineage identity towards AR(+) adenocarcinoma. Conclusions: These data support our hypothesis that NSD2 inhibition can reverse NEPC to AR(+) adenocarcinoma lineage and restore sensitivity to standard-of-care ARPI. Given these mechanistic insights and the safety profile observed with our NSD2 inhibitor in the clinic, evaluation of NSD2 inhibition in NEPC patients is warranted.
Evaluating the impact of a community-based prostate cancer screening program.
Authors: Amy Leader, Kristine Pham, Nicola Cianci, Fatuma Doka, Suzanne Barron, Katie Bradley, Oleksandr Kolesnikov, Jordan DeHoratius, Olivia Dahlgren, Le'Ann Robles, Robert Giamboy, Hannah Knapp, Leonard G. Gomella
Journal: Journal of Clinical Oncology (2025)

324 Background: One out of eight men in the U.S. will be diagnosed with prostate cancer during his lifetime. Early detection, often by routine screening, allows for more options for treatment and an increased chance of survival. Barriers to screening exist and may contribute to prostate cancer disparities, particularly among Black males and those who lack regular access to health care. Community based screening programs may be an effective way to overcome barriers to prostate cancer screening. Methods: An urban, NCI-designated cancer center collaborated with community partners and a national prostate cancer advocacy organization to provide free screening to males in our catchment area. Community partners identified the location of the screening and promoted the event. Participants completed a survey about their personal and family history of prostate cancer. A mobile screening team within the cancer center conducted the screenings, consisting of prostate specific antigen (PSA) tests. All participants received a letter with their PSA test results; males with an abnormal result (&gt; 3 ng/mL) also received a phone call. Survey data was analyzed with descriptive statistics and bivariate analyses (ANOVA). Results: Two hundred and eighty-nine (n=289) males were screened at a community screening event. The mean age of males screened was 57.3 (SD=11.2) and the majority identified as Black (N=253, 84.9%). The mean PSA test value was 1.82 (SD= 2.70); 14% of males had an abnormal PSA test result. Black males had the highest PSA values of among all men who were screened. Conclusions: Disparities in prostate cancer, particularly among Black males, warrant interventions like community-based prostate screening events that reduce barriers of cost and access, bringing screening to those who would most benefit. Mean PSA test results by patient characteristics. N Mean PSA Level Sum of Squares, DF Between Groups Within Groups F p Full Sample 298 1.82 Race/Ethnicity 3; 19.62 271; 1876.18 0.94 0.42 Black 246 1.85 Hispanic 18 0.80 White 9 1.48 Other 2 1.59 PSA in the last 3 years, # tests 3; 19.43 260; 1861.65 0.91 0.44 0 121 1.62 1-3 133 1.82 4-6 6 3.40 7+ 4 2.08 Family history of PCa, # of relatives 2; 54.09 287; 2051.72 3.78 0.024* 0 215 1.78 1 63 1.50 2+ 12 3.84 Family history of PCa genetic risk, # of relatives 2; 11.75 287; 2094.06 0.81 0.45 0 229 1.71 1 52 2.24 2+ 10 1.96 Smoking status 4; 31.74 256; 1815.53 1.12 0.35 Current 26 2.19 Former, quit within 10 years 8 0.93 Former, quit within 11-19 years 8 1.46 Former, quit more than 20 years ago 20 2.75 Never 199 1.68 Diet, fat intake 2; 9.49 272; 1888.09 0.68 0.51 Low 60 1.65 Medium 186 1.71 High 29 2.29 Chemical Exposure 1; 2.80 257; 1824.87 0.39 0.53 Not exposed 210 1.72 Exposed 49 1.97 *Indicates significance (p &lt;0.05).
Impact of pre-existing diabetes mellitus on acute care use in older patients with metastatic prostate cancer on androgen receptor signaling inhibitors.
Authors: Michael A. Liu, Rohit R. Raghunathan, Karie Runcie, Shikun Wang, Jason Dennis Wright, Alexander Z Wei, Mark N. Stein, Dawn L. Hershman
Journal: Journal of Clinical Oncology (2025)

119 Background: Androgen receptor signaling inhibitors (ARSIs) are mainstay treatments for metastatic prostate cancer. Hyperglycemia is a common side effect but limited data exists on outcomes such as hospitalizations in patients with diabetes mellitus (DM) starting on ARSIs. Methods: We used the SEER-Medicare linked data for patients aged 66 and older with de novo metastatic prostate cancer who were prescribed abiraterone, enzalutamide, or apalutamide per part D files from 2011 to 2019. Eligible patients had continuous Medicare Part A/ B coverage before and after drug initiation, and Part D coverage before initiation. Patients were excluded if they died within 6 months of diagnosis or received chemotherapy prior to ARSI (&lt;1%). Univariate associations between covariates and DM were assessed using chi-square tests or t-tests. Negative binomial regression was used to calculate incidence rate ratios of acute care use (total number of hospital or emergency admissions divided by total time at risk) for each model covariate among DM and non-DM patients after initiation of ARSI. Results: 2697 patients met eligibility criteria, of which 17.4% (469) had DM. The average age of the cohort was 75.0 years ±7.0 SD. 85.3% (2300) of patients received androgen deprivation therapy (ADT) prior to ARSI, and 0.9% (24) received ADT afterwards. 28.3% (773) of patients received abiraterone only, 23.8% (641) received only enzalutamide or apalutamide, and 47.6% (1283) received both treatments. Patients with DM (vs without) differed significantly with regards to lower high school education, higher NCI comorbidity score (excluding DM), and less receipt of abiraterone, but not in age, race, marital status, prior ADT treatment, or receipt of enzalutamide or apalutamide. 29.5% (797) of patients had acute care use within 6 months, with 39.9% (187) in the DM group and 27.4% (610) in the non-DM group ( p &lt;.0001), Adjusted for covariates, patients with DM had a 41% increased rate of acute care use ( p =0.0016) compared to those without DM. Additionally, compared to those prescribed only enzalutamide or apalutamide, patients prescribed abiraterone had a 47% increased rate of acute care use ( p =0.0026); this was independent of having DM (interaction p =0.77). Conclusions: Patients with pre-existing DM on ARSIs experienced higher rates of acute care use compared to those without DM, regardless of ARSI type. Future studies should assess potential interventions in older patients with diabetes on ARSIs, such as close monitoring of glycemic status or adherence to risk reduction medications.
ctDNA characterization in mCRPC patients with pathogenic germline variants.
Authors: Tivoli Nguyen, Nicholas Habibian, Akerele Opeoluwa, Olivia Pocha, Priya Bhandari, Courtney Johnson, Minqi Huang, Alexandra Lieberman, Jennifer Schwartz, Jodi Lyn Layton, Brian E. Lewis, Alton Oliver Sartor, Elisa Marie Ledet
Journal: Journal of Clinical Oncology (2025)

247 Background: Approximately 10% to 15% of men with metastatic castration-resistant prostate cancer (mCRPC) harbor germline mutations. Circulating tumor-derived DNA (ctDNA) as non-invasive approach to characterizing somatic alterations. In this study, we report longitudinal ctDNA assessments in mCRPC patients who have undergone germline testing. Methods: A total of 238 patients, who had undergone both germline testing and ctDNA assessment from Tulane Cancer Center were included in this study. Germline testing was conducted using a multi-gene cancer panel from Invitae, covering 50-86 genes, while somatic alterations in ctDNA were tested through Guardant 360, including 70-83 genes. Somatic alterations with &lt;0.1%, synonymous, and variants of unknown significance were excluded from analyses. Statistical analyses were performed using Pearson Chi-Square Test or Fisher Exact Test. Results: From 2015-2024, 17.2% (41/238) had pathogenic or likely-pathogenic (P/LP) germline mutations. The most common pathogenic germline mutations were in BRCA2 (17.1%; 7/41), BRCA1 (9.8%; 4/41), and CHEK2 (9.8%; 4/41). In ctDNA, germline positive patients were more likely to have frameshift mutations (OR= 1.75, 95% C.I. [1.09, 2.81], p=0.02) and less likely to have copy number amplifications (OR= 0.58, 95% C.I. [0.36, 0.93], p= 0.03) compared to germline negative patients. Among mCRPC patients with germline HRR P/LP mutations, frameshift alterations were significantly more frequent (OR=5.03, 95% CI [2.03, 13.23], p-value=0.0008). mCRPC patients with germline P/LP mutations were more likely to have somatic mutations in BRCA2 (OR=2.85; 95% CI: [1.62, 4.93]; p=0.0002) and GATA3 (OR=3.37, 95% CI: [1.26, 8.51]; p=0.016) detected ctDNA and less likely to have EGFR alterations (mutations and/or amplifications) (OR=0.46; 95%CI: [0.25, 0.80]; p=0.0094). BRCA2 somatic mutations are also more likely to be detected in patients with germline P/LP mutations in HRR genes (OR=0.11, 95% CI [0.03, 0.33], p=0.00004). Conclusions: mCRPC patients with pathogenic germline mutations are more likely to have frameshift and less likely to have copy number amplifications compared to germline negative mCRPC patients. Frameshift mutations are more likely to be detected in patients with germline P/LP in HRR genes. Patients with germline P/LP mutations are more likely to have somatic mutations BRCA2 and GATA3 and less likely to have mutations and/or amplifications in EGFR.
Ethnic disparities in clinical trials for FDA-approved drugs in prostate cancer: A post–COVID-19 era analysis (2020-2024).
Authors: Bruno R. Bastos, Michael A. Schwartz, Oleg Gligich, Jacqueline Claudia Barrientos, Antonio Ramirez-Ridelli, Leonardo Borregales, Alan Nieder, Akshay Bhandari, Debra Linzer, Nicolas Kuritzky, Mike Cusnir
Journal: Journal of Clinical Oncology (2025)

25 Background: It is known that ethnic and racial inequality in participation in oncology clinical trial is a contemporary problem. Efforts have been made by NCI and FDA to address cancer disparities as per new policies placed in 2017. Despite these efforts, there are still disparities in cancer treatment and clinical trial participation. There is paucity of data in participation of minorities in the post COVID-19 era of the FDA approved agents in Prostate Cancer. Methods: From 2020-2024, a total of 4,744 patients participated in the seven clinical trials (MAGNITUDE, TALAPRO-2, VISION, PROPEL, ARASENS, HERO, PROfound and TRITON3) that led to FDA approval of new agents or indications to treat patients with prostate cancer. All clinical trials were industry-sponsored. We assessed and tabulated the reporting of racial demographics within these trials employing chi-square statistics and machine learning algorithms to compare participation rates among White, Black, Asian and Hispanic patients against SEER data on prostate cancer incidence. Results: Among the eight trials, five (ARASENS, MAGNITUDE, PROPEL, TALAPRO, TRITON-3) reported racial data in White, Asian and Black participants, but only one reported data on Hispanics (MAGNITUDE). Our analysis revealed that in the five trials providing racial data, 68% were White indicating statistically significant overrepresentation (p&lt;0.001), Black participation was only 3% signifying statistically significant underrepresentation with (p&lt;0.0001). In the only trial with data in Hispanics, there was a 12.1% participation of Hispanics with no significant disparity observed (p=1). Conclusions: Lack of representation of minorities persist in post COVID area FDA approved drugs clinical trials in prostate cancer. Lack of a more comprehensive data in race have also been seen in recent trials. Further implementation of policies for better data capture and standardization in the nomenclature of ethnicity should be pursued. Additionally, in international collaboration trials, a separate data on US participants utilizing NCI SEER data ethnicity nomenclature should be considered.
Efficacy and safety of fexagratinib (Fexa) in Chinese patients (pts) with metastatic or unresectable urothelial carcinoma (mUC) harboring FGF receptor (FGFR) genetic alterations.
Authors: Xiaojie Bian, Shanshan Wang, Dingwei Ye, Shaoxing Zhu, Xin Gou, Benkang Shi, Jun Xiao, Bin Hu, Xianling Liu, Shusuan Jiang, Haitao Liu, Chaohong He, Xiaoping Zhang, Zhiwen Chen, Xinli Kang, Changfu Li, Ning Xu, Yong Yang, Kun Li, Qilin Wang
Journal: Journal of Clinical Oncology (2025)

790 Background: Fexagratinib (former AZD4547), a selective and potent oral inhibitor of FGFR1-3, has shown promising efficacy and safety in phase I trials among solid tumor pts with FGFR1-3 alterations, including mUC. This study (NCT05086666) aimed to assess efficacy and safety of Fexa in previously treated Chinese mUC pts with FGFR alterations. Methods: Pts with mUC harboring FGFR3 alterations (including activating mutations or fusion detected via NGS panel) who failed at least 1 prior therapy or were platinum- ineligible, were enrolled. Pts received continuous oral Fexa 80mg BID until disease progression or unacceptable toxicity occurred. The primary endpoint was objective response rate (ORR) assessed by independent review committee (IRC) per RECIST v1.1. Results: As of data cutoff (14 Jun 2024), a total of 35 pts were enrolled, of those 80% were male with a median age of 66 years (range 41-86). Most pts (85.7%) had ECOG PS≤1, 43% had a creatinine clearance &lt;60 mL/min, 66% had received ≥ 1 prior therapies, 66% had been treated with PD-(L)1. The primary tumor site was reported in the upper tract in 40% of pts, and 25.7% had liver metastases. The best overall responses assessed by IRC was 34.4% (95% CI, 18.6%-53.2%) in 32 evaluable pts, including 9 confirmed partial responses (cPRs), 2 unconfirmed PRs. Ten (37.0%) of 27 evaluable pts harboring FGFR3 mutation achieved at least one PR. Among 15 pts who experienced progression after PD-(L)1 treatment, 5 pts (33.3%) achieved cPRs. Median PFS by IRC was 3.6 (2.8, 6.1) months. Most common treatment-related adverse events (TRAEs) were anemia (40.0%), nail disorder (40.0%), hyperphosphatemia (37.1%) and hyponatremia (34.3%). Grade ≥3 TRAEs were reported in 54.3% of the pts, incidence &gt;5% included pneumonia(5.7%), anemia (5.7%) and hand-foot syndrome (5.7%). Conclusions: Fexa was generally well tolerated in previously treated Chinese mUC pts, with no new safety signals identified. The efficacy observed was consistent with that previously reported in western populations, with notable benefits seen in pts with FGFR alterations who had experienced disease progression following PD-(L)1 treatment. Clinical trial information: NCT05086666 .
Precision diagnostics in prostate cancer treatment (PREDICT): A phase 2 multi-arm biomarker-based study (Alliance A032102).
Authors: Rana R. McKay, Glenn Heller, Shuang Zhao, Elizabeth Marie Wulff-Burchfield, Dhaval Shah, Alan Tan, Matthew D. Galsky, Jonathan E. Rosenberg, Himisha Beltran
Journal: Journal of Clinical Oncology (2025)

TPS281 Background: Advances in genomic sequencing have allowed for a deeper understanding of the molecular complexity of metastatic castration resistant prostate cancer (mCRPC) with several actionable alterations now identified, fueling new biomarker-based treatment strategies. For this reason, it is recommended that all patients with mCRPC undergo germline and somatic tumor profiling. In addition to DNA aberrations, gene expression changes can capture actionable targets and activated pathways. The phase 2 PREDICT trial is using both DNA and RNA aberrations to select patients with mCRPC for rationally-designed biomarker-based therapeutic strategies. Methods: This is a multi-center, multi-arm, biomarker-driven phase 2 umbrella study with a primary objective of objective response rate for patients with mCRPC and measurable disease. Secondary objectives include radiographic progression-free survival, PSA response, time to first symptomatic skeletal event, overall survival, safety, and correlative studies. Eligible patients must have progressive mCRPC of any histology, received a prior androgen receptor pathway inhibitor (ARPI), and received or refused taxane chemotherapy. Patients with measurable and non-measurable disease are eligible. Patients must have standard of care next generation DNA sequencing via any CLIA-certified tissue or circulating tumor DNA assay for initial trial enrollment. For arm allocation based on RNA alterations, testing will be via the CLIA-certified Caris MI Tumor Seek assay, which includes whole exome and whole transcriptome sequencing, derived from tissue obtained within 12 months of enrollment. A real-time molecular tumor board will convene to review genomic reports and confirm arm allocation on a rolling basis as biomarker results become available. Patients with Rb loss (DNA), Rb functional loss signature (RNA), NEPC signature (RNA) will be allocated to treatment with the EZH1/2 inhibitor valemetostat. Patients with at least 2 of 3 tumor suppressor gene DNA alterations (TP53, RB1, PTEN), FANC alteration (DNA), or SLFN11 overexpression (RNA) will be allocated to cabazitaxel plus carboplatin. Patients without any study-defined alterations will be allocated to physician choice treatment with either cabazitaxel, ARPI, or 177 Lu-PSMA-617. The study is designed to accommodate future biomarker arms. A maximum of 64 patients with measurable disease and 94 patients with non-measurable disease for a total of 158 patients, will be accrued to each treatment arm. This Simon two-stage minimax design has a type 1 error equal to 0.05 when the probability response is 0.20 and has power of 0.90 if the probability of response is 0.37. Clinical trial information: NCT.