bluuebunny/crossref_metadata_2025_split huggingface dataset:
TRIUMPH: Phase II trial of rucaparib monotherapy in patients with metastatic hormone-sensitive prostate cancer harboring germline DNA repair gene mutations.
Authors: Markowski Mark Christopher , Sternberg Cora N. , Wang Hao , Sullivan Rana , King Serina , Lotan Tamara L. , Antonarakis Emmanuel S. 
Published: March 2023

190 Background: Androgen deprivation therapy (ADT) is the backbone of treatment for patients (pts) with metastatic prostate cancer (PCa), but many pts find this difficult to tolerate. Treatment with non-castrating regimens may avoid or delay the toxicities of hormonal therapy. The activity of PARP inhibitors (PARPi) in pts with homologous recombination DNA-repair (HRD) mutations (muts) and metastatic castration-resistant PCa has been established. We hypothesized here that the benefit of ARPi can be maintained in the absence of ADT in a biomarker-selected (HRD mutated) population with PCa. We designed a Phase 2 study in men with hormone-naïve, metastatic PCa who harbored a germline HRD mut treated with rucaparib monotherapy (without ADT). Methods: This was a multi-center, single arm Phase 2 study (NCT03413995) in men with asymptomatic hormone-sensitive metastatic PCa who received rucaparib 600mg by mouth daily. During consenting, pts were informed and had to opt out of ADT-based therapy. Pts must have had a germline mutation in an HRD gene on clinical-grade testing. The primary endpoint was confirmed PSA50 response rate. Key secondary endpoints included safety, objective response rate (ORR), and radiographic progression-free survival (rPFS). The trial was designed to detect a 25% absolute increase in PSA50 response from a null of 50%. Results: 12 pts were enrolled, 7 with BRCA1/2 and 5 with CHEK2 muts. The confirmed PSA50 response rate to rucaparib was 41.7% (N=5/12, 95% CI: 19.3-68.1%), which did not meet the pre-specified efficacy boundary to enroll additional patients to 2nd stage. In pts with measurable disease, the ORR was 60% (N=3/5, all with BRCA2). Median rPFS on rucaparib was 10.3 months (95% CI: 4.0 mo - NR). At the time of the interim analysis, 3 pts remained on study. The majority of adverse events (AE) were Grade ≤2 and expected. Translational studies are ongoing. Conclusions: Rucaparib can induce clinical responses in a biomarker-selected PCa population without concurrent ADT. However, the pre-specified threshold of PSA50 response was not met. Although durable responses were observed in a subset of pts, PARPi without ADT in metastatic hormone sensitive PCa will not be pursued. Clinical trial information: NCT03413995 . [Table: see text]
Early outcomes from lutetium Lu-177 vipivotide tetraxetan treatment in patients selected for therapy with piflufolastat F-18 PET imaging.
Authors: Boike Thomas Pence , DiPippo Vincent A. , Austin Heather , Turnquist Wendy , Qamruzzaman Yusuf 
Published: March 2023

191 Background: The Vision trial utilized Ga 68 PSMA 11 imaging to select patients for treatment with Lutetium Lu 177 Vipivotide Tetraxetan. Current guidelines allow not only Ga 68 PSMA 11 PET but also Piflufolastat F 18 PET when selecting patients for Lutetium Lu 177 Vipivotide Tetraxetan but little is published on outcomes to this approach. Methods: Patients were enrolled on an IRB approved managed access protocol and were treated by a single investigator at a single institution. Eligible patients had mCRPC and had received previous treatment with at least one androgen receptor pathway inhibitor and at least one round of taxane based chemotherapy. Baseline imaging, demographics, treatment history, and tumor characteristics were collected. Patients were treated with 7.4 GBq of Lutetium Lu 177 Vipivotide Tetraxetan every 6 weeks for up to six cycles. Adverse events and PSA response were collected. Results: Fourteen patients were enrolled between August 2021 and August 2022. All patients had advanced mCRPC, were heavily pre-treated, and had failed both hormonal as well as chemotherapeutic options. The average number of androgen receptor pathway inhibitor courses for the cohort is 2.4 (range 1-4) and the average number of taxane courses for the cohort is 1.5 (Range 1-3). 11 patients underwent Piflufolastat F 18 PET and 3 patients had Ga 68 PSMA 11 PET. Baseline PSA varied significantly from 2.51 - 961.71 ng/mL. Declines of 50% in PSA were observed in 8/14 patients. 2 patients had greater than 80% PSA reductions. Conclusions: PSA treatment responses were similar to those reported in the Vision trial in this cohort of patients selected with either Piflufolastat F 18 PET or Ga 68 PSMA 11 PET supporting the guideline recommendations. Clinical trial information: NCT04825652 .
Real-world assessment of AR-LBD mutations in metastatic castration-resistant prostate cancer.
Authors: Antonarakis Emmanuel S. , Zhang Nicole , Saha Jayati , Nevalaita Liina , Shell Scott A. , Garratt Chris , Ikonen Tarja , Fizazi Karim 
Published: March 2023

204 Background: Treatment of men with metastatic castration-resistant prostate cancer (mCRPC) using drugs targeting the AR pathway is hampered by development of resistance including activating AR ligand-binding domain (LBD) point mutations. AR LBD mutations are found in approximately 10-20% of patients (pts) with mCRPC progressing on AR pathway inhibition (ARPi) therapy and may be associated with AR activation by alternative steroid hormones. We utilized the Guardant INFORM real-world database to explore the detection rate and clinical features associated with AR-LBD mutations in men with mCRPC. Methods: This observational study was conducted in a nationally representative clinical-genomic database of 200,000+ advanced cancer pts undergoing comprehensive ctDNA analysis (Guardant360, Redwood City, CA) between 2014 and 2021, with associated clinical information from administrative claims. ctDNA samples of men with mCRPC were assessed for presence or absence of an activating AR-LBD mutation. The incidence of co-occurring genetic alterations was also investigated. Clinical outcomes were studied for matched cohorts comparing pts following first line (1L) or second line (2L) mCRPC therapy with or without AR-LBD mutations. Results: Of 15,705 prostate cancer pts included in the database, 8420 (53.6%) had mCRPC at the time of sample collection. 4122 (49.0%) of these mCRPC pts had prior treatment with an ARPi, of which 854 (21%) had an AR-LBD mutation. AR-LBD mutation prevalence was 15% in mCRPC pts untreated with an ARPi, 23% in those after 1 line, and 24% in those after 2 lines of ARPi treatment. AR L702H and T878A/S showed the greatest increase in prevalence post abiraterone, whereas AR L702H, T878S and F877L had the greatest increase in prevalence post enzalutamide. Prevalence of AR L702H and H875Y doubled (from 8.8% to 17.5%) for pts that received chemotherapy post ARPi, while AR F877L incidence declined by half (3.5% to 1.7%). Compared to pts without AR-LBD mutations, AR-LBD+ mCRPC pts were enriched for co-alterations in APC, CTNNB1, PTEN, BRCA2, and ARID1A. Rates of TP53 and RB1 alterations were comparable in the AR-LBD+ and ARLBD- cohorts. Matched mCRPC pts had similar time-to-treatment-discontinuation (TTD) and time-to-next-treatment (TTNT) between AR-LBD+ and AR-LBD- mCRPC pts in the 1L and 2L settings; however, AR-LBD+ pts exhibited worse overall survival from 1L mCRPC therapy (50.1 vs 60.7 months, log-rank P=0.013). Conclusions: In this large database, the overall detection rate of activating AR-LBD mutations in men with mCRPC undergoing ctDNA analysis was 21%, and increased with prior use of 2nd generation ARPi (abiraterone and enzalutamide). Men with AR-LBD mutations were more likely to harbor other alterations relevant to tumor progression. These findings inform on the ctDNA prevalence and impact of AR-LBD mutations in a real-world dataset of mCRPC.
Prognostic biomarkers and clinical outcomes in neuroendocrine prostate cancer (NEPC).
Authors: Gagnon Richard , Khosh Kish Ealia , Cook Sarah , Takemura Kosuke , Cheng Brian Yu Chieh , Bressler Kamiko , Heng Daniel Yick Chin , Alimohamed Nimira S. , Ruether Joseph D. , Lee-Ying Richard M. , Bose Pinaki , Kolinsky Michael Paul , Vasquez Catalina , Samuel Divya , Lewis John D , Faridi Rehan , Borkar Minal , Fairey Adrian S. , Bismar Tarek A. , Yip Steven M. 
Published: March 2023

209 Background: NEPC includes both pure small cell carcinoma and mixed tumors with varying degrees of adenocarcinoma and neuroendocrine histology. It arises de novo or is treatment associated (TA) post androgen deprivation therapy. Clinical outcome data and prognostic biomarkers are limited and were thus explored. Methods: Patients with high grade prostate cancer and morphologic and/or immunohistochemical (IHC) NEPC features were included in this retrospective multicentre study. Clinical stage, Gleason score, and serum biomarkers were recorded. Kaplan-Meier method and log-rank test calculated and compared overall survival (OS) from time of NEPC diagnosis.Cox proportional hazards regression assessed prognostic impact of serum biomarkers at diagnosis and de novo vs TA status, adjusting for clinical stage and castration resistance. Results: 135 NEPC cases were identified. 124 (92%) were mixed tumors. 56 (41%) arose de novo. 79 (59%) were TA. 77% of those with a Gleason score (N=85/110) were grade group 5. Median PSA pre-NEPC biopsy was 11.6 ng/mL. At NEPC diagnosis, 19 (14%) had localized disease (median OS 123.0 mo); 33 (24%) non-metastatic castrate-sensitive disease (median OS 42.3 mo); 6 (4%) non-metastatic castrate-resistant disease (median OS 14.3 mo); 35 (26%) metastatic castrate-sensitive disease (median OS 17.6 mo); and 42 (31%) metastatic castrate-resistant disease (median OS 9.6 mo). Median OS for those with visceral metastases was 8.6 mo (95% CI 6.0 – 14.6), compared to patients with non-visceral metastases (11.1 mo; 95% CI 13.7 – 21.5) and no metastases (42.3 mo; 95% CI 47 – 89). Anemia (adjusted HR 1.66; 95% CI 1.05 - 2.16, p = 0.031) and NLR >3 (adjusted HR 1.51; 95% CI 1.01 - 2.52, p = 0.045) were associated with increased risk of death. De novo disease, elevated LDH, serum PSA, and Gleason score were not prognostic. Conclusions: This study identifies NEPC clinical outcomes by stage, with survival poorer than expected in pure prostate adenocarcinoma. Anemia and elevated NLR >3 are prognostic biomarkers that may help risk stratify and guide treatment intensification, including platinum-based chemotherapy. Further biomarker characterization of NEPC through IHC-staining pattern and genomic analysis is currently underway by this group.
Healthy lifestyle, Agent Orange exposure, and inherited PCa risk: An analysis of the Million Veteran Program.
Authors: Pagadala Meghana , Lui Asona , Lynch Julie Ann , Karunamuni Roshan , Lee Kyung Min , Plym Anna , Rose Brent S. , Carter Hannah , Kibel Adam S. , DuVall Scott L. , Gaziano J. Michael , Panizzon Matthew , Hauger Richard , Seibert Tyler M 
Published: March 2023

210 Background: Prostate cancer (PCa) risk is understood to be mostly unmodifiable and inherited, but there is evidence that environmental and behavioral factors may also contribute. A recent study of health professional cohorts suggests a healthy lifestyle can mitigate a high inherited risk of lethal PCa. It is unknown how modifiable factors affect PCa risk in more diverse populations. Our objective was to determine the effects of healthy lifestyle and Agent Orange exposure on PCa risk when accounting for race/ethnicity, family history, and genetic risk in a diverse population. Methods: The Million Veteran Program (MVP) is a national, population-based cohort study of United States military veterans conducted 2011-2021 with 590,750 male participants available for analysis. Healthy lifestyle was quantified as: A healthy lifestyle score (range 0-3) was calculated with a point assigned for each of the following at MVP enrollment: not a current smoker, body mass index (BMI) 30 and strenuous activity 2 days per week. Agent Orange exposure was obtained from VA records. Genetic risk was assessed via a polygenic hazard score using genotype data. Results: Healthy lifestyle was independently associated with reduced metastatic PCa (HR 0.82, 95% CI 0.77–0.87, p<0.001) and fatal PCa (HR 0.76, 95% CI 0.68–0.86, p<0.01) when accounting for family history, genetic risk, and race/ethnicity. The benefit of healthy lifestyle was also observed in Black participants on subset analysis. Agent Orange exposure was an independent factor for PCa diagnosis (HR 1.06, 95% CI 1.04-1.09). Conclusions: Adherence to a healthy lifestyle is associated with reduced risk of metastatic or fatal PCa, which offsets inherited risk.
Nivolumab plus ipilimumab for the treatment of post-chemotherapy metastatic castration-resistant prostate cancer (mCRPC): Additional results from the randomized phase 2 CheckMate 650 trial.
Authors: Sharma Padmanee , Krainer Michael , Saad Fred , Castellano Daniel , Bedke Jens , Kwiatkowski Mariusz , Patnaik Akash , Procopio Giuseppe , Wiechno Pawel , Kochuparambil Samith Thomas , Thomas Christian , Arranz Arija Jose Angel , McCune Steven L. , Hansen Steinbjorn , Daugaard Gedske , Amin Neha P. , Wang Yumeng , David Justin M. , Pachynski Russell Kent 
Published: March 2023

22 Background: In preliminary analyses from the randomized phase 2, open-label CheckMate 650 trial, nivolumab (NIVO) 1 mg/kg (N1) plus ipilimumab (IPI) 3 mg/kg (I3) Q3W × 4 doses showed clinical activity in patients (pts) with post-chemotherapy (post-CT) mCRPC, particularly those with high tumor mutational burden (TMB), but early toxicity contributed to treatment discontinuations. Here, we report results from pts with post-CT mCRPC receiving alternative NIVO+IPI dosing regimens vs IPI alone vs cabazitaxel (CABA) in CheckMate 650. Methods: Newly enrolled pts previously treated with docetaxel for mCRPC were randomized 2:2:1:2 to cohorts D1 (NIVO 3 mg/kg [N3] + IPI 1 mg/kg [I1] Q3W × 4 doses then NIVO 480 mg Q4W), D2 (N1 Q3W × 8 doses + I3 Q6W × 4 doses then NIVO 480 mg Q4W), D3 (I3 Q3W × 4 doses), or D4 (CABA 20 or 25 mg/m2 Q3W + prednisone 10 mg × 10 doses). Crossover from cohorts D3 and D4 to cohort D1 was allowed after radiographic progressive disease. Outcomes included safety, objective response rate (ORR), prostate-specific antigen response rate (PSA-RR; confirmed PSA decline ≥ 50% from baseline), radiographic progression-free survival (rPFS) per blinded independent central review (BICR), and overall survival (OS). Associations between efficacy and TMB were assessed. Results: Overall, 259 pts were randomized (D1, n = 73; D2, n = 74; D3, n = 38; D4, n = 74). Median (range) follow-up for OS was 23.3 (6.0–31.5) months. In the NIVO+IPI cohorts (D1 and D2), median duration of therapy was 2.8 and 2.4 months; the median number of IPI doses received was 4 and 2, and 15% and 26% of pts discontinued due to study drug toxicity, respectively. Two pts died due to study drug toxicity (1 each in cohorts D1 and D2). Key safety and efficacy data are shown. Several pts in cohorts D1 and D2 showed notable reductions (75-100%) in tumor size and PSA. Approximately one-third of pts in cohorts D3 and D4 crossed over to D1. Based on preliminary analyses in small numbers of evaluable pts, there was no clear and consistent association between efficacy and tissue or blood TMB in the NIVO+IPI cohorts (D1 and D2). Conclusions: These results further support the clinical activity of NIVO+IPI in select pts with post-CT mCRPC. Detailed evaluations of the characteristics of responders to NIVO+IPI, including more expansive biomarker analyses, are warranted. Clinical trial information: NCT02985957 . [Table: see text]
A comparative analysis of patients presenting with optic canal metastasis of prostate cancer.
Authors: Kelkar Neil , Wang Jue 
Published: March 2023

23 Background: Prostate cancer (PCa) is the second-most diagnosed cancer and the second leading cause of cancer deaths in United States Males. Due to an emphasis on early detection of PCa, only a small percentage present with distant disease. We report cases of ocular metastasis of PCa, a late finding of PCa. Methods: Systematic review of the literature and pooled analysis of published cases of PCa with optic canal or orbital metastasis, including one from our institution. A subgroup analysis compared those who presented with optic metastases as their initial presentation (IP) versus those who presented with optic metastases after diagnosis (AD). Results: 39 patients with ocular metastasis of PCa were selected for this study. Twenty-one cases (53%) presented with ocular metastasis in the initial presentation, and 18 presented with an optic canal metastasis after diagnosis. The overall average age was 66 years (45-85 years). The average age for the IP group was 70 years (59-85 years) and 62 years (45-70 years) for the AD group. Metastatic sites varied between cases. Nineteen cases (49%) presented with widespread lesions involving the axial skeleton, with 8 IP cases (44%) versus 11 AD cases (52%). Ten cases (26%) involved solitary metastases to the optic nerve, optic disc, choroid, or orbit, with 5 IP cases (2%) versus 5 AD cases (24%). Three cases (7.5%) presented with bilateral orbital metastases. One case (2.5%) involved bilateral solitary lesions to the optic nerves. The common complaints patients presented with were proptosis (33%), diplopia (26%), decreased visual acuity (41%), and vision loss (10.3%). Thirty-seven cases reported primary adenocarcinoma on histology (95%). Thirty cases reported mortality data, with 16 reporting patient death after diagnosis. Of these, 6 cases (out of 12) report death from PCa in the IP group, and 10 cases (out of 18) report death from PCa in the AD group. Conclusions: Despite early prostate cancer screening increases, patients can present with distant metastasis as their initial presentation. We recommend prompt tumor molecular/genetic testing to inform targeted treatment when faced with atypical cases.
Disparities in prostate cancer diagnoses in persons experiencing homelessness.
Authors: Mayo Zachary S , Parker Sean M. , Kilic Sarah S , Weleff Jeremy , Strzalka Colleen , Phelan Michael P. , Mian Omar Y. , Stephans Kevin L. , Suh John H. , Tendulkar Rahul D. 
Published: March 2023

24 Background: We previously reported that persons experiencing homelessness (PEH) are significantly less likely to undergo prostate specific antigen (PSA) testing compared to persons not experiencing homelessness (non-PEH). The purpose of this study was to determine if reduced PSA testing in PEH results in more advanced prostate cancer diagnoses. Methods: We identified PSA screening eligible PEH (men ages 50-69) from an institutional registry of all patients that presented to our healthcare system as homeless from 2014 to 2021. A matched cohort of non-PEH was generated for comparison. Institutional CPT and HCPCS billing codes for PSA testing were available beginning 01/01/2017 and cross-referenced to identify PEH and non-PEH who underwent PSA testing at least once between 01/01/2017 and 12/31/2021. In patients with ≥ 1 PSA test, we recorded screening, oncologic and treatment related variables. Patients with a history of prostate cancer diagnosed outside the study timeframe were excluded. Results: A total of 9,249 PEH were identified, with 1,597 meeting PSA screening criteria during the study timeframe; 3,370 screening eligible non-PEH were available for comparison. The median age was 59.0 for PEH and 60.0 for non-PEH. PEH were significantly less likely to have a primary care provider (58% vs 81%, p<0.001) or to have a PSA test (12% vs 33%, p<0.001). Among patients with a PSA test, PEH were significantly less likely to have multiple PSA tests compared to non-PEH (28% vs 61%, p<0.001) and significantly more likely to have a PSA ≥ 4.0 (18% vs 12%, p=0.028). In patients with a PSA ≥ 4.0, PEH were less likely to receive a prostate biopsy (37% vs 61%, p =0.009) and there was a trend towards decreased prostate MRI (11% vs 25%, p=0.085). A total of 6 PEH (0.4%) and 46 non-PEH (1.4%) were diagnosed with prostate cancer. The median PSA at diagnosis was 12.6 in PEH vs 7.0 in non-PEH (p=0.052). PEH were significantly more likely to present with high/very high risk disease (4/6 [66%] vs 9/46 [20%], p=0.019); no PEH had very low/low risk disease compared with 20 (43.5%) non-PEH. PEH were more likely to present with lymph node positive or metastatic disease (3/6 [50%] vs 3/46 [7%], p=0.016). The median time from biopsy to treatment was 119 days in PEH and 76 days in non-PEH (p=0.391). Conclusions: PEH are less likely to receive prostate cancer testing following an elevated PSA and more likely to present with high risk advanced prostate cancer. Interventions to increase prostate cancer awareness in PEH are needed to reduce disparities.
Racial differences in survival and healthcare resource utilization among Medicaid-insured adults with metastatic castration-sensitive prostate cancer.
Authors: DerSarkissian Maral , Gupta Deepshekhar , Ivanova Jasmina , Niyazov Alexander , Zanardo Enrico , Guo Tracy , Wang Jingru , Duh Mei Sheng , Freedland Stephen J. 
Published: March 2023

26 Background: Racial inequalities in healthcare have long existed in the United States, with Black or African American (BAA) men having higher overall cancer death rates compared to other racial or ethnic groups. One of the greatest disparities is in prostate cancer (PC), which disproportionately affects BAA men, though when matched for stage, whether outcomes differ by race is controversial. This study assessed differences in overall survival (OS) and healthcare resource utilization (HRU) by race in Medicaid-insured patients with metastatic castration-sensitive prostate cancer (mCSPC). Methods: This retrospective longitudinal cohort study evaluated de-identified administrative claims data from the Centers for Medicare and Medicaid Services 100% Medicaid data files, from 01/01/2010 - 12/31/2018. The study included adult patients with a diagnosis for PC, ≥1 claim for androgen deprivation therapy (ADT), diagnosis of metastasis before or within 90 days after ADT, and continuous eligibility for ≥6 months pre-index (defined baseline period) and ≥3 months post-index. The date of first receipt of ADT or first receipt of novel hormonal therapy or docetaxel if initiated within 30 days before ADT defined the index date. OS and HRU were assessed from the index date to the earliest of end of continuous eligibility, data availability, or death. A multivariable Cox proportional hazards model of OS and a multivariable Poisson model of HRU were implemented and controlled for age, plan type, region, median state income, residence in a state with Medicaid expansion, index year, Charlson comorbidity index (CCI), baseline HRU, and clinical characteristics. Results: The study included 1,488 patients with mCSPC (467 [31%] BAA, 446 [30%] White [W], 219 [15%] Hispanic [H], 356 [24%] Other races [O]). H were the oldest (mean age 68 years), followed by O (67 years), W (64 years), and BAA (63 years). BAA and H had the highest CCI (0.6), followed by O (0.5), and W (0.4). Median unadjusted OS was 71.3 months in H, 57.1 months in O, 52.1 months in BAA, and 44.9 months in W. After adjustment, H had significantly lower risk of death compared to W (hazard ratio [95% confidence interval (CI)]: 0.65 [0.43, 0.96]) and BAA patients had comparable survival to W (0.91 [0.69, 1.22]). Adjusted incidence rate ratios (IRR) showed significantly lower incidence of PC-related outpatient (OP) visits for BAA as compared to W (IRR [95% CI]: 0.71 [0.55, 0.99]), per patient per year. The remaining HRU endpoints were not significantly different among racial groups. Conclusions: Among Medicaid-insured adult patients with mCSPC, H were more likely to live longer than W patients. BAA patients had similar survival and lower rates of PC-related OP visits as compared with W, which shows differential use of PC-related healthcare resources between BAA and W.