bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment (tx) patterns among men with metastatic castration resistant prostate cancer (mCRPC) in the United States (US).
Authors: Barata Pedro C. , Leith Andrea , Ribbands Amanda , Montgomery Rachel , Last Matthew , Arondekar Bhakti , Niyazov Alexander , Ivanova Jasmina 
Published: February 2022

52 Background: Novel hormonal therapies (NHTs) and docetaxel were initially approved for the tx of men with mCRPC. Over time, these agents moved earlier in the disease continuum and are now also used in metastatic castration sensitive prostate cancer (mCSPC). Little is known about first-line (1L) mCRPC tx patterns for men with prior taxane-based chemotherapy (CT) or NHT exposure. This study evaluated the impact of taxane CT or NHT use in mCSPC on recent 1L tx patterns among men with mCRPC in the US. Methods: Participating physicians collected information from medical charts for the next consecutive 4 adult men with mCRPC during January-August 2020. A subset of men had prior mCSPC tx information available. 1L mCRPC txs were described overall and stratified by previous tx with taxane CT or NHT during mCSPC. No statistical comparisons were performed. Results: 116 adult men with mCRPC and known mCSPC tx history were included. Mean age was 70 years; 15% had known family history of prostate cancer; 70% had bone metastases and 33% had visceral metastases at data collection. Overall, 10% (12/116) of men had been previously treated with taxane CT and 28% (32/116) were treated with NHT during mCSPC. 1L mCRPC tx was initiated on average 35 days after mCRPC diagnosis. NHT was the most common 1L mCRPC tx regardless of prior taxane CT or NHT use. Men pre-treated with taxane CT were more likely to initiate mCRPC tx with NHT than taxane naïve men. NHT pre-treated men were less likely to initiate 1L mCRPC tx with NHT and more likely to initiate tx with docetaxel than NHT naïve men. 53% of men with prior NHT tx were rechallenged with NHTs in 1L mCRPC. (Table). Conclusions: Findings from this US real-world study among men with mCRPC suggest physicians most commonly initiate 1L mCRPC life-prolonging tx with NHT regardless of prior taxane CT or NHT exposure. Additional studies with larger sample sizes are needed to confirm these findings and better understand optimal tx sequencing, especially as new tx options become available.[Table: see text]
Use of bone modifying agents for metastatic castrate-resistant prostate cancer.
Authors: Mitchell Aaron Philip , Meza Akriti Mishra , Farooki Azeez , Panageas Katherine , Bach Peter B. , Lipitz-Snyderman Allison , Morris Michael J. 
Published: February 2022

55 Background: Bone modifying agents (BMAs) prevent skeletal related events (SREs) among patients with metastatic, castrate-resistant prostate cancer (mCRPC) involving the bone. The utilization of BMAs among patients with mCRPC and bone metastasis has not been well defined, and the number of patients who may benefit but are undertreated is not known. We conducted this study to measure patterns of BMA among mCRPC patients. Methods: We used linked SEER cancer registry and Medicare claims data. Our cohort included men newly diagnosed with de-novo stage IV prostate adenocarcinoma during 2007-2015, with followup through 2016. We included those age > = 66 at diagnosis, had continuous enrollment in Medicare Parts A and B from 180 days prior to diagnosis through the outcome period and Part D from diagnosis through outcome period, and who received androgen deprivation therapy. We further limited the cohort to those who subsequently received a CRPC-defining therapy (eg., abiraterone, sipuleucel-T, docetaxel if occurring prior to CHAARTED trial results). We grouped the cohort according to those who did vs. did not have evidence of bone metastasis in claims. Our primary outcome was receipt of a BMA (zoledronic acid or denosumab) within 180 days of initiating a CRPC-defining therapy. Among patients who received BMAs after initiating CRPC therapy, we further characterized the time at which they first initiated a BMA. Results: Our sample included 1,303 patients, of which 85% had evidence of bone metastasis. Overall, 58% received a BMA within 180 days of initiating a CRPC-defining therapy. 66% of patients with evidence of bone metastasis received BMAs, compared to 16% of those without evidence. Of patients who received BMAs, 38% first received BMAs between 90 days prior to starting CRPC therapy and 180 days after; the remaining 62% were previously receiving BMAs during the castrate-sensitive phase of disease. Among patients with evidence of bone metastasis who initiated CRPC-defining therapy in 2007-2009, 65% received BMAs; this proportion was 69% and 64% for those began CRPC therapy during 2010-2013 and 2014-2016, respectively. Conclusions: Approximately two-thirds of patients with mCRPC and bone metastases received BMAs within 180 days of initiating a CRPC-defining therapy. In most cases BMA therapy was initiated while patients still had castrate-sensitive disease, for which BMAs are indicated only at lower doses for the prevention of osteoporotic fractures. Further work is needed to understand whether real-world dosing is in line with clinical indications, and whether the one-third of patients who did not receive BMA therapy appropriately reflects the proportion of patients with contraindications. Further work is also needed to characterize patient and provider factors associated with appropriate BMA use.
Preliminary results of the "DUO" observational study: Quality of life assessment and cross-sectional follow-up of prostate cancer patients treated with degarelix.
Authors: Roupret Morgan , Rozet Francois , Delattre Diane Dalila , Lacour Hugo , Ghassan Fallouh , Durand Matthieu , Mongiat Artus Pierre 
Published: February 2022

62 Background: The use of androgen deprivation therapy (ADT), has increased over time in the treatment of prostate cancer (PCa). ATD is accompanied by side effects, some of which may increase the cardiovascular (CV) risk. The aim of this study was to evaluate the prevalence of cardiovascular risks and quality of life at the initiation of degarelix, a GnRH antagonist, and 6 months later, in patients with advanced hormone-sensitive PCa. Methods: The DUO study is a PASS, pharmaco-epidemiologic, longitudinal, multicenter observational study. It prospectively enrolled PCa patients during the first 6 months of treatment with degarelix. cohort to describe the prevalence of real-life cardiovascular co-morbidities in. The study was carried out in 46 French urology centers. At D0 and M6, the prevalence of CV, osteoporotic, metabolic, mood disorder, geriatric and sexual morbidity and risk factors were recorded using validated tools and questionnaires. EQ-5D questionnaire measured quality of life. The evolution of the disease (PSA levels) and the tolerance of the treatments were also reported. Results: A total of 124 patients with advanced hormone-dependent PCa (of whom 26.6% were metastatic) were included. At D0 57.7% of patients had a CV morbidity and CV risk factors. Metabolic co-morbidities were also present in 60.6% of patients, osteoporotic risk factors in 34%, sexual disorders in 58%, and mood disorders in 36%. ONCO-G8 score ≤ 14 was observed in 45.6% of patients aged ≥ 70 years. The percentage of patients with CV co-morbidities remained stable (56.7%). The rates of osteoporotic, metabolic, sexual, and mood-related morbidity and risk factors also remained unaltered. Likewise, quality of life remained stable between D0 and M6 (Scores: 0.765 and 0.813 respectively). At the same time, the median PSA rate decreased by -98.4% from D0 (p < 0.001). 42 adverse events (AEs) were reported in 22 patients: degarelix-related AEs were reported in 4.4% of patients. Conclusions: The results of the DUO study showed high prevalence of CV co-morbidity and risk factors in patients with advanced PCa. It also showed no significant increase in CV co-morbidities and risk-factors during the first 6 months of treatment with degarelix as it was observed for osteoporotic, metabolic, sexual, and mood-related disorders. The GnRH antagonist was well tolerated without major impact on quality of life. Assessment of multiple co-morbidities at the initiation and during ADT is mandatory for the optimal management of patients.
Correlation of the rate of metastasis-free survival with the presence of pathogenic germline genetic mutations in patients with prostate cancer at a community practice.
Authors: Ramanathan Siddharth , Ramanathan Sadhna , Martinez Alvaro , Korman Andrew , Ghilezan Michael , Levin Michael , Gerndt Zachary Alan , Shen Nathan , Wojno Kirk , Korman Howard , Balaraman Savitha 
Published: February 2022

70 Background: Loeb et al. recently highlighted that academic physicians were statistically more likely to recommend genetic testing to prostate cancer patients per NCCN guidelines compared to physicians at community practices. Several articles have outlined the rate of pathogenic mutations and metastasis free survival (MFS) for prostate cancer patients treated at academic institutions. However, there is a relative paucity of equivalent data regarding patients treated at community urology clinics. We felt it was important to retrospectively review data from our large community based uro-oncology practice and present our findings in an effort to clarify this topic. Methods: We collected data on 562 prostate cancer patients treated at our multidisciplinary uro-oncology clinic between 2016 and 2018. We found 363 patients that satisfied the inclusion criteria of having germline genetic mutation testing and at least 1 year of follow-up. Patients were stratified into three categories based on the results of their germline genetic test: negative for germline mutations, positive for germline pathogenic mutations, or positive for VUS (variant of uncertain significance) mutations. Analysis of variances (ANOVA) was conducted to assess for any differences in age, Gleason score, metastasis rate, and MFS across the groups. A significance level of.05 was used. Results: All patients were treated according to guideline recommendations as was standard for the practice. There was no statistically significant difference in average age or Gleason score between the groups. There was also no statistically significant difference between the MFS across the three groups. Although the metastasis rate and MFS in the group without any mutations (9.8%, 18.3 months) was clinically significant compared to the groups with pathogenic mutations (7.5%, 16.5 months) and VUS mutations (7%, 16.6 months), the differences were not statistically significant (p=.754 and.127 respectively). Conclusions: In our community based uro-oncology practice, we found no statistically significant difference in MFS between patients with pathogenic germline mutations, patients without germline mutations, and patients with VUS mutations at 1 year of follow-up. This does not exclude the possibility of an impact of germline mutations on MFS as the data matures to reach 5 or more years of follow-up.[Table: see text]
Phase 1 study of PSCA-targeted chimeric antigen receptor (CAR) T cell therapy for metastatic castration-resistant prostate cancer (mCRPC).
Authors: Dorff Tanya B. , Blanchard Suzette , Martirosyan Hripsime , Adkins Lauren , Dhapola Gaurav , Moriarty Aidan , Wagner Jamie R , Chaudhry Ammar , D'Apuzzo Massimo , Kuhn Peter , Forman Stephen J. , Priceman Saul 
Published: February 2022

91 Background: Chimeric antigen receptor (CAR)-engineered T cell therapies are being pursued for the treatment of mCRPC. Prostate Stem Cell Antigen (PSCA) is highly expressed on the surface membrane in mCRPC and with limited expression on normal tissues. We undertook a phase 1, first-in-human study of a PSCA-targeted 4-1BB-co-stimulated CAR T cell therapy in mCRPC. Methods: CAR T cells were manufactured at City of Hope’s cGMP facility. The trial followed the Target equivalence range design with an equivalence range of.20-.35 and too toxic level of 0.51 following participants in cohorts of 3. The plan was to begin at a dose of 100 million (M) without lymphodepletion (LD) chemotherapy consisting of fludarabine and cyclophosphamide, then add LD to 100M prior to dose escalation to maximum 600M. Patients (pts) were required to have disease progression after at least 1 androgen receptor targeted therapy but there was no limit on prior chemotherapy or other treatments. Primary objective is to define the dose limiting toxicity (DLT) and recommended phase 2 dose as well as to describe preliminary bioactivity and efficacy. Correlative studies include MRI for target bone lesion response, CAR T cell persistence, circulating tumor cells, and serum cytokines. Results: 12 pts have been treated to date, median age 68 (42-72). Three pts were treated at the 100M dose with no DLTs. In the 100M plus LD dose level there 2 pts experienced DLT of grade 3 cystitis non-infective and fatigue. The protocol was amended to reduce the LD dose to 300 mg/m2 cyclophosphamide D1-3 and intensify monitoring with early intervention for cystitis. No DLT occurred in 3 pts treated in the modified LD 100M cohort. Cytokine release syndrome (CRS), DLTs and best response by RECIST are presented by dose level in the table. PSA declines (one >90%) were seen as well as radiographic improvement, though RECIST response was limited to stable disease (SD) by concurrent bone metastases. Correlative studies indicated bioactivity of PSCA-CAR T cells. Conclusions: PSCA-CAR T cell therapy is feasible in pts with mCRPC with DLT of cystitis, and shows preliminary anti-tumor effect at a dose of 100M plus LD. Dose escalation to 300M may proceed. Clinical trial information: NCT03873805. [Table: see text]
Safety evaluation of M9241 in combination with docetaxel in metastatic prostate cancer.
Authors: Atiq Mohammad O. , Chandran Elias Bin Aris , Meininger Luke , Karzai Fatima , Bilusic Marijo , Marte Jennifer L. , Arlen Philip M. , Cordes Lisa M. , Strauss Julius , Redman Jason , Floudas Charalampos S. , Pastor Danielle M. , Owens Helen , Hankin Amy , Williams Monique , Figg William Douglas , Dahut William L. , Schlom Jeffrey , Gulley James L. , Madan Ravi Amrit 
Published: February 2022

93 Background: M9241 is an immunocytokine that targets single- and double-stranded DNA which allows the treatment to localize IL-12 to necrotic tumor (Xu, CCR 2017). M9241 was well-tolerated as a monotherapy in a Phase I study with solid tumors (Strauss J, CCR 2019). Additional preclinical data has demonstrated synergy of M9241 with cytotoxic therapy. This is the first study to examine the safety of a novel combination of chemotherapy and immunocytokines in metastatic prostate cancer. Methods: This safety analysis included patients with mCSPC or mCRPC. Patients were enrolled in a 2-dose level (DL) escalation cohort of M9241 (DL 1: 12mcg/kg, DL 2: 16.8mcg/kg) combined with docetaxel (75mg/m2) with 6 patients planned per DL. A third DL of 8mcg/kg will enroll 6 more patients after the 16.8mcg/kg DL has fully enrolled. All patients were treated with ADT. Patients were initiated on treatment with docetaxel with a plan for mCSPC patients to receive six 3-week cycles of combined treatment and mCRPC patients to continue until progression or unacceptable toxicity. M9241 was given starting with the second cycle of treatment for each patient. Dose-limiting toxicity (DLT) was evaluated in the first 6 weeks after start of docetaxel (from cycle 1 day 1 through the end of the first cycle with M9241). Results: The study has enrolled 10 patients out of a planned 18 for the safety portion. Age range is 58-82 with a median of 69 years. Race distribution is 80% White and 20% Black. Gleason scores for patients were 8 (40%), 9 (40%), and 10 (20%). No DLTs were seen with either dose-level. Only 1 patient had a Grade 4 AE, neutropenia. Grade 3 toxicities included anemia, diarrhea, leukopenia, and hypotension (each occurring in 10% of the patients). The most frequent adverse events (AEs) of any grade were anemia (40%) and lymphopenia (40%), followed by fatigue (30%), diarrhea (20%), and fever (20%). Conclusions: We established a safe dose-level of M9241 at ≥ 12mcg/kg. Updated clinical data from the safety cohort (n = 18) will be presented. This demonstrates that an immunocytokine and chemotherapy can be safely combined for treatment in metastatic prostate cancer. A planned expansion cohort will evaluate docetaxel and M9241 in mCRPC. Clinical trial information: NCT04633252.
Phase 2 trial of immunotherapy in tumors with CDK12 inactivation (IMPACT): Results from cohort A of patients (pts) with metastatic castration resistant prostate cancer (mCRPC) receiving dual immune checkpoint inhibition (ICI).
Authors: Alva Ajjai Shivaram , Li Jinju , Chou Jonathan , Reimers Melissa Andrea , McKay Rana R. , Zhang Jingsong , Daignault-Newton Stephanie , Palmbos Phillip Lee , Reichert Zachery R , Cieslik Marcin , Chinnaiyan Arul , Abida Wassim 
Published: February 2022

103 Background: Prostate cancer with CDK12 inactivation represents a distinct subtype in mCRPC, tumors are characterized by excessive tandem duplications, genomic instability, gene fusion-caused putative neoantigens and increased tumor T cell infiltration. Retrospective experiences with ICI in CDK12 inactivation CRPC pts reported PSA and radiographic responses. We conducted a prospective multi-site clinical trial of ipilimumab and nivolumab in CDK12 inactivation or mutated cancers. Herein, we report our findings in the completed cohort A of men with mCPRC. Methods: Eligible pts had mCRPC (ongoing androgen deprivation therapy with serum testosterone £ 50 ng/dL) and putative CDK12 inactivation of function aberrations on any commercial or institutional CLIA/CAP approved next generation sequencing assay. Archival tumor tissue was requested for correlative biomarker analysis. Pts received nivolumab 3 mg/kg IV and ipilimumab 1 mg/kg IV q3 weeks for up to 4 cycles, followed by maintenance nivolumab at 480 mg IV q4 weeks until disease progression, intolerable toxicity, or consent withdrawal. The primary endpoint was PSA response, defined as a greater than or equal to 50% decline in PSA from baseline. Secondary endpoints included safety/toxicity, secondary efficacy measures including QoL and overall survival. Exploratory objectives included baseline tumor whole exome analysis and changes in circulating immune profiles with therapy. Results: As of data cut-off in Aug 2021, 28 mCRPC pts enrolled in Cohort A; median ECOG PS was 1 (0-2 range), 22/28 had Gleason 8-10 cancer, mean baseline PSA at study entry was 231 ng/dL, all pts had received ≥1 prior oral androgen signaling inhibitor and ≥1 cytotoxic chemotherapy. Unconfirmed PSA ≥30% decline was seen in 6/28 pts (21.4%) and PSA ≥50% decline in 4/28 pts (14.2%). Grade ≥3 possible/probable/definite adverse events were noted in 7/28 (25%) and SAEs in 10/28 pts (35.7%). Six pts (21.4%) experienced a rapid PSA increase by ≥ 10-fold over baseline. Conclusions: Combination immunotherapy was reasonably tolerated in this heavily pre-treated population and was associated with unconfirmed PSA responses in a subset of pts. Ongoing correlative analyses could explain responses mechanistically. Enrollment in Cohort B of non-prostate cancers and Cohort C of nivolumab monotherapy in prostate cancer are still ongoing. Clinical trial information: NCT03570619.
Cohort study of oligorecurrent prostate cancer patients: Oncological outcomes of patients treated with salvage lymph node dissection via PSMA radioguided surgery.
Authors: Maurer Tobias , Mehdi Irai Mehrdad , Rauscher Isabel , Simon Ricarda , Eiber Matthias , van Leeuwen Fijs WB , van Leeuwen Pim , Budaeus Lars , Steuber Thomas , Graefen Markus , Tennstedt Pierre , Heck Matthias , Horn Thomas , Knipper Sophie 
Published: February 2022

106 Background: Prostate-specific membrane antigen (PSMA) positron-emission tomography (PET) allows detection of small and/or atypically localized metastatic prostate cancer (PCa) lesions. In a subset of patients with recurrent oligometastatic PCa salvage surgery with PSMA-targeted radioguidance (PSMA-RGS) may be of value. We aimed to evaluate the oncological outcomes of salvage PSMA-RGS for oligorecurrent PCa and determine predictive preoperative factors of improved outcomes. Methods: In this cohort study within two tertiary care centers, patients with biochemical recurrence (BCR) after radical prostatectomy (RP) and imaging with PSMA PET receiving salvage PSMA-RGS between 2014 and 2020 were analyzed. Kaplan-Meier and multivariable Cox regression models adjusted for various parameters were used to test for BCR-free survival (BFS) and therapy-free survival (TFS) differences. Postoperative complications were classified according to Clavien-Dindo. Results: Overall, 364 patients were assessed. At PSMA-RGS, median (IQR) age and preoperative PSA was 67 (61-71) years and 1.0 (0.5-1.9) ng/ml. Metastatic soft-tissue lesions were removed in 356 (94.4%) patients. Within three months from surgery, 25 (6.6%) patients suffered from Clavien-Dindo complications grade III-IV. During follow-up, 235 patients experienced BCR and 129 patients received further therapy. Median follow-up for patients who did not experience BCR and who did not receive further therapy was 11.1 months and 10.5 months, respectively. Median (IQR) BFS and TFS was 7.8 (5.4-10.9) and 34.9 (24.7-43.5) months. At two years of follow-up, BFS rate was 31.9% and TFS rate was 56.6%. In multivariable analyses, higher preoperative PSA (HR: 1.06), higher number of PSMA-avid lesions on preoperative imaging (HR: 1.2) and multiple (pelvic plus retroperitoneal) localizations (HR: 1.7), as well as retroperitoneal localization (HR: 2.0) of lesions in PSMA PET imaging were independent predictors of BCR after PSMA-RGS. Limitations are the retrospective design and lack of a control group. Conclusions: As salvage surgery in oligorecurrent PCa currently constitutes an experimental treatment approach careful patient selection is mandatory based on life expectancy, low PSA values and low number of PSMA PET avid lesions located in the pelvis. Further studies are needed to confirm our findings and define the oncological value of salvage surgical procedures in oligorecurrent PCa.