bluuebunny/crossref_metadata_2025_split huggingface dataset:
Real-world treatment patterns among patients with metastatic castration-resistant prostate cancer (mCRPC) in the US.
Authors: Malangone-Monaco Elisabetta , Li Weiyan , Noxon Virginia , Jiang Shan , Amin Suvina , Ghate Sameer , Swami Umang , Agarwal Neeraj 
Published: February 2022

49 Background: mCRPC is an incurable disease with poor prognosis. Though multiple treatments such as novel hormonal therapies (NHT: abiraterone [abi], enzalutamide [enza], docetaxel [doce], cabazitaxel [caba], sipuleucel-T [Sip-T] etc.) are approved, real-world data regarding treatment sequencing are lacking. This study assesses the real-world treatment patterns within the context of FDA-approved life-prolonging treatments for mCRPC. Methods: The IBM MarketScan database was used to identify newly diagnosed (incident) mCRPC patients from 1/1/2014-5/31/2020. Adult males were required to have a diagnosis of PC, and subsequently evidence of metastasis and castration (medical or surgical). Incident mCRPC status (index) was determined 3 ways: 1) treatment with an NHT within 3 months after castration and an FDA-approved mCRPC treatment ≥3 months after NHT; 2) first FDA-approved treatment ≥6 months after castration; 3) first FDA-approved treatment 3-6 months after castration and a second FDA-approved treatment ≥3 months after treatment. Lines of therapy (LOT) were measured in the variable-length follow-up of ≥1 month and consisted of all drugs observed within 28 days of first observed treatment. Duration of therapy was measured as start of line to start of next line or end of enrollment. Results: A total of 2,912 mCRPC patients met all study criteria and received ≥1 LOT. Among those, 48.7% had ≥2 LOT, and 21.8% had ≥3 LOT. Patients were an average age of 71 years at index and used leuprolide (87%), abi (10%), doce (9%) and enza (8%) prior to index. In mCRPC the most common observed first line (1L) monotherapy regimens were abi (35%), enza (34%), and doce (14%). The most common observed second-line (2L) treatments were enza (36%), abi (27%), and doce (14%). Mean duration of 1L was 292 days compared to 245 days in 2L. The most frequently observed treatment sequences (1L to 2L) are reported in the table. Opioids (62%) and denosumab (47%) use was common in mCRPC patients. Conclusions: Among mCRPC patients, NHTs were the most common 1st and 2nd LOTs and alternate NHT after a first NHT was the most common sequence. With rapidly evolving treatment options in metastatic prostate cancer, these data can help guide estimation of eligible patients for different clinical trials. Further studies are needed to understand the high attrition from 1L to subsequent lines of therapy, the reasons for treatment preference and impact on clinical outcomes with different treatment sequencings.[Table: see text]
Real-world experience with relugolix.
Authors: Kasparian Saro , Wei Oren , Lehmer Christopher , Pal Sumanta K. , Lyou Yung , Dorff Tanya B. 
Published: February 2022

57 Background: Gonadotropin-releasing hormone (GnRH) antagonists were developed in part to avoid testosterone flare to achieve faster and more consistent testosterone suppression. Relugolix (Rel) was given FDA approval for use in prostate cancer (PCa) based on the phase 3 HERO trial but some real-world concerns include compliance, affordability, and performance in patients transitioning from another GnRH agent or in combination with other therapeutic agents. The aim of our study was to evaluate the real-world implications of prescribing and/or switching to Rel. Methods: A single institution retrospective study was conducted on patients prescribed Rel. Treatment data including concomitant therapeutic agents were collected. Compliance data was measured via chart review and pharmacy dispensary records. Patients were classified as either newly castrated or transitioning from another agent. PSA and testosterone levels were tabulated. Reported adverse effects (AE), and reasons for discontinuation if applicable including financial toxicity were noted. Results: 50 patients were reviewed; 15 (30%) treated for adjuvant, 18 (36%) for biochemical recurrence, and 17 (34%) for metastatic PCa. 12% were on concomitant therapy with abiraterone, 4% with enzalutamide, and 2% with apalutamide. 80% reported compliance to Rel. 5 (10%) never filled the prescription. 30 (60%) were newly castrated (castration restart or naïve) while 16 (36%) were transitioned from another GnRH. No changes in PSA or testosterone were noted in patients switched form injected GnRH to Rel. The most common documented AE effects included hot flashes 24%, fatigue, 29%, and weight gain 9%. No unexpected toxicity was reported in combination with abiraterone. Of 11 patients who discontinued therapy, 45% did so due to cost, 36% due to AE, and 27% due to therapy completion. 4 of 16 (25%) of those who transitioned from injection GnRH felt symptoms were worse on Rel. Conclusions: In our early experience with Rel, patients did comply to therapy based on self-reporting, pharmacy fill dates, and laboratory evidence of castration. However, financial toxicity was and remains a significant barrier both accessing Rel and remaining on Rel therapy. While a differential toxicity was reported by those who switched from injection GnRH, sometimes leading to discontinuation, there were no new safety signals reported, especially in combination with abiraterone.
Clinical annotations for prostate cancer research: Defining data elements, creating a reproducible analytical pipeline, and assessing data quality.
Authors: Keegan Niamh M. , Vasselman Samantha E , Barnett Ethan , Nweji Barbara , Carbone Emily , Blum Alexander , Morris Michael J. , Rathkopf Dana E. , Slovin Susan F. , Danila Daniel Costin , Autio Karen A. , Scher Howard I. , Kantoff Philip W. , Abida Wassim , Stopsack Konrad H. 
Published: February 2022

64 Background: Routine clinical data from the electronic medical record are indispensable for retrospective and prospective observational studies and clinical trials. Their reproducibility is often not assessed. We sought to develop a prostate cancer-specific database with a defined source hierarchy for clinical annotations and to evaluate data reproducibility. Methods: At a comprehensive cancer center, we designed and implemented a clinical database for men with prostate cancer and clinical-grade paired tumor–normal sequencing for whom we performed team-based retrospective clinical data annotation from the electronic medical record, using a prostate cancer-specific data dictionary. We developed an open-source R package for data processing. We then evaluated completeness of data elements, reproducibility of team-based annotation using blinded repeat annotation by a medical oncologist as the reference, and the impact of measurement error on bias in survival analyses. Results: Data elements on demographics, diagnosis and staging, disease state at the time of procuring a genomically characterized sample, and clinical outcomes were piloted and then abstracted for 2,261 patients and their 2,631 genomically profiled samples. Completeness of data elements was generally high, between 55% to 99% for elements of clinical TNM staging, self-reported race, biopsy Gleason score, and presence of variant histologies, both for the team-based annotation and the repeat annotation. Comparing team-based annotation to the repeat annotation (100 patients/samples), reproducibility of annotations was high to very high. For 7 binary data elements, both sensitivity and specificity of the team-based annotation reached or exceeded 90%. The T stage, metastasis date, and presence and date of castration resistance had lower reproducibility. Impact of measurement error on estimates for strong prognostic factors was modest. Conclusions: With a prostate cancer-specific data dictionary and quality control measures, manual team-based annotations can be scalable and reproducible. The data dictionary and the R package for reproducible data processing tools provided (https://stopsack.github.io/prostateredcap) are freely available to help increase data quality in clinical prostate cancer research.
The changing landscape of treatment and survival for men with castration-resistant prostate cancer in the era of novel treatments.
Authors: Caram Megan Veresh , Kumbier Kyle , Tsao Phoebe A. , Burns Jennifer A. , Sparks Jordan , Bauman Jordan , Stensland Kristian , Hollenbeck Brent K. , Shahinian Vahakn B. , Skolarus Ted A. 
Published: February 2022

67 Background: Several therapies for men with castration-resistant prostate cancer (CRPC) have become available since 2010 with the hope of prolonging survival for those at the end stages of their disease. Little is known about the survival of men who receive novel therapies in the real world and the disease burden of patients initiating treatment for CRPC between 2010 and 2017. Methods: Using the Veterans Health Affairs Corporate Data Warehouse, we identified Veterans with CRPC who received first-line therapy for castration-resistant disease between 2010-2017. Therapies included ketoconazole, docetaxel, abiraterone, and enzalutamide since > 99% of patients treated for CRPC received one of these therapies first-line for CRPC. We used a Cox model to calculate the overall survival of patients from time of first CRPC treatment for each year. We then adjusted for patient and disease characteristics, such as starting PSA level, and prognostic group at the start of treatment based on hemoglobin, alkaline phosphatase, and albumin levels. Results: In a cohort of 4,998 men started on treatment for CRPC between 2010-2017, survival from start of first-line treatment gradually increased between 2010-2017. In 2010, when 38% of men received docetaxel first-line and 62% ketoconazole, the probability of surviving at least one year from start of first-line therapy was 64%. In 2017, when the landscape of first-line treatment had changed (49% abiraterone, 9% docetaxel, 41% enzalutamide, 1% ketoconazole) one-year survival from start of first therapy improved to 72%. The unadjusted hazard ratio (HR) for an additional calendar year was 0.93 (95% confidence interval [CI], 0.91-0.95). Men started on first-line CRPC therapy in 2010 had worse prognostic labs at the start of therapy, suggesting worse disease, and had a higher PSA value at the start of therapy compared to those started on CRPC therapy in 2017 (median PSA 55.1 in 2010 vs 27.8 in 2017, p-value < 0.01). When adjusting for disease characteristics, the improvement in survival we saw between 2010 and 2017 was diminished with adjusted HR for an additional calendar year of 0.97 (95% CI, 0.94-1.00). Conclusions: With the development of novel therapies, the survival of patients with similar disease burden should gradually improve over time. Although we did see a modest improvement in survival between 2010-2017, this improvement was mitigated when adjusting for disease severity, suggesting that some of the improvement in survival may be affected by a lead-time bias—treating patients earlier in their CRPC.
First look at patient reported outcomes from IRONMAN, the international registry of men with advanced prostate cancer.
Authors: Rencsok Emily , George Daniel J. , Kantoff Philip W. , Villanti Paul , Vinson Jake , Gerke Travis A. , Hyslop Terry , Mucci Lorelei A 
Published: February 2022

69 Background: While population-based estimates of advanced prostate cancer survivors are lacking, an estimated 180,000 men in the US are living with metastatic prostate cancer. Their survivorship experience is distinct from localized patients as they suffer quality of life detriments both due to the severity of disease and its therapies. We examined quality-of-life indictors among men in the IRONMAN global registry of advanced prostate cancer. Methods: IRONMAN (International Registry of Men with Advanced Prostate Cancer) is a population-based prospective study of men with newly diagnosed advanced, metastatic hormone-sensitive (mHSPC) and castration-resistant prostate cancer (CRPC) enrolled from 16 countries. We report data from first 1865 men enrolled, 1567 who completed a baseline Patient Reported Outcome Measure (PROM) in the US (N=581), Canada (N=245), Spain (N=166), UK (N=204), Australia (N=126), Switzerland (N=88), Sweden (N=70), Ireland (N=46), and Brazil (N=41). PROMs are collected at baseline and every three months using electronic (90%) or paper versions of validated questionnaires. Results: The cohort includes 1,128 men with mHSPC and 737 with CRPC. Based on self-report, 9% of men overall (18% in the US) are Black and 83% are white (78% in the US). Sleep problems were common among men at enrollment, with 59% of men reporting problems with insomnia. The prevalence was similarly high among men with mHSPC or CRPC disease. Ten percent of men reported that pain substantially interfered with daily activities, and 24% reported pain had some effect. Physical functioning was high among both mHSPC (median 93.3, 80-100) and CRPC (median 86.7, 73.3-100) patients based on EORTC QLQ-30. Global health status was similar between the two groups (median 75, 58.3 - 83.3). More than 25% of men reported some cognitive impairment at baseline. Financial difficulties due to the disease and treatment were quite high, ranging from 12% in Sweden, 16% in Canada and Spain, 34% in the US, and 46% in Brazil. Conclusions: Men with advanced prostate cancer experience a range of quality of life detriments which impair overall health. While at baseline, many of these measures were similar among men with mHSPC and CRPC, we will continue to monitor these over time to examine changes in quality of life associated with disease progression and treatments. A longer-term goal is to identify opportunities for intervention to improve quality of life and potentially improve survival. Clinical trial information: NCT03151629.
Association of functional outcomes by decision-making approach in men with metastatic prostate cancer (mPC).
Authors: Schumacher Frank , Helenowski Irene B. , Moses Kelvin A. , Benning James , Morgans Alicia K. 
Published: February 2022

78 Background: Multiple treatments with similar efficacy exist for mPC resulting in multifaceted treatment choices. Shared decision-making (SDM) engages patients and may be associated with superior outcomes in men with prostate cancer. We assessed the association of decision locus of control (DLOC) (SDM vs. physician- or patient-directed decisions) and measures of patient quality of life (QOL), including patient reported functional outcomes, and decision satisfaction. Methods: Patients completed surveys of decision-making practices after a clinic visit in which a decision occurred. Patients also completed the EORTC QLQ-C30 QOL instrument at baseline (time of decision), and 2- and 4-months. Scores for each QOL dimension and pain were calculated for each time point, and the least-squared means were compared among DLOC groups to evaluate for associations using a mixed effects model. Results: 101 patients participated, with median age of 69 years [range: 49-92]. Most patients were white (80%) and married (82%). A majority of patients reported experiencing SDM in the clinic visit assessed (63, 62%). At baseline, there was no significant difference in patient reported QOL dimensions among DLOC groups, but patients reporting physician-directed decisions reported significantly greater baseline pain than the SDM group (Table). At 4 months, patient reported physical functioning was superior among patients reporting patient-directed (p=0.005) or SDM (p=0.03) than those who reported physician-directed decision-making. There was a trend toward greater decision satisfaction among patients who reported patient-directed (p=0.06) or SDM (p=0.10) at 4-months compared to men reporting physician-directed decision-making. There were no differences at 4 months for social, emotional, cognitive, or role functioning between DLOC groups. Conclusions: Patients who reported greater control during treatment decisions had superior physical functioning and a trend toward greater decision satisfaction at 4 months compared with patients reporting physician-directed decisions, suggesting measurable domains of benefit from involvement in the decision-making process. Continued research evaluating the association between physical and psychological outcomes and DLOC is needed, including larger studies within more diverse populations.[Table: see text]
Targeting resistant prostate cancer, with or without DNA repair defects, using the combination of ceralasertib (ATR inhibitor) and olaparib (the TRAP trial).
Authors: Reichert Zachery R , Devitt Michael Edward , Alumkal Joshi J. , Smith David C. , Caram Megan Veresh , Palmbos Philip , Vaishampayan Ulka N. , Alva Ajjai Shivaram , Braun Thomas , Yentz Sarah Elizabeth , Tsao Phoebe A. , Dreicer Robert , Cackowski Frank Cameron , Shah Neel , Dean Emma , Smith Simon , Heath Elisabeth I. 
Published: February 2022

88 Background: Men with metastatic, castration resistant prostate cancer (mCRPC) harboring DNA repair defects (̃20%) achieve a radiographic progression free survival of 7.4 months with PARP inhibitors (PARPi). Preclinical studies combining a PARPi (olaparib) and DNA damage checkpoint inhibitor (ATR inhibitor, ceralasertib) show synergy, providing the rationale to test this combination in men with mCRPC, including where single agent olaparib has been shown to be active. Methods: Two cohorts were accrued to a trial combining ceralasertib with olaparib in men a) with or b) without DNA repair defects. All patients progressed on ≥1 prior mCRPC therapy with no prior PARPi or platinum chemotherapy. The primary endpoint was disease response (confirmed PSA decline ≥50% and/or RECIST response), while disease progression was defined per Prostate Cancer Working Group 3 definition. Each cohort is analyzed independently for disease endpoints, while both groups were combined for toxicity assessments. Results: The 12 person DNA repair-deficient (DRDef) cohort allowed patients with germline BRCA2 loss (n = 4), somatic BRCA2 loss (n = 1) and ATM loss (n = 1 germline, n = 5 somatic and n = 1 somatic with unknown germline). 35 men without BRCA2/BRCA1 or ATM genomic loss were accrued to the DNA repair-proficient (DRPro) cohort. These men had next-generation sequencing (NGS) on contemporary biopsies (prior to enrolment without intervening therapy, 12), prior NGS on metastatic tissue (10), prior NGS on primary prostatic tissue (n = 3), or cell-free analyses (5). Five patients have incomplete cell-free analyses. At data cutoff (October 2021), in the DRDef cohort, the response rate by confirmed ≥50% PSA decline was 4/10 (40%) including 3 of 4 BRCA2 patients, and another is awaiting sufficient follow up; 1 of 6 ATM-deficient patients responded and another is awaiting sufficient follow up. All 4 DRDef responders remain on therapy (median of 8 months). For patients in the DRPro cohort who have completed therapy and response assessment (n = 21), 3 responded, one with a duration of 12 months, two with 6 months. An updated analysis will be presented. Conclusions: This analysis suggests potential activity of the doublet for DRDef (BRCA2 mainly) and DRPro mCRPC. Ongoing biomarker analysis (e.g. ATM IHC, contemporaneous cell-free DNA analysis rather than archived tissue) may help guide selection of patients most likely to benefit. Clinical trial information: NCT03787680.
Evaluation of drug-drug interactions among patients with metastatic prostate cancer in routine care.
Authors: Gassian Noemie , Clairet Anne-Laure , Goujon Morgan , Frontczak Alexandre , Calcagno Fabien , Almotlak Hamadi , Mouillet Guillaume , Maurina Tristan , Stein Ulrich , Nguyen Thierry , Jeannin Marie , Thiery-Vuillemin Antoine 
Published: February 2022

111 Background: Prostate cancer often occurs in an elderly population, at higher risk of drug-drug interactions (DDIs). There is a medical need to increase the knowledge of DDI prevalence and their severity among patients coming from routine care. This study used a prospective approach with the aim to quantify and describe DDIs in medical prescription of prostate cancer treatments. Methods: DDIs were assessed from two perspectives: 1) “real DDI” between the patient’s comedications and the actual anti-cancer agent prescribed; 2) “modelized DDI” between the patient’s comedications and drugs that have proven activity in metastatic endocrine sensitive prostate cancer (MESPC) or castrate resistant prostate cancer (CRPC) settings with positive phase 3 trial and gained EMA approval. French national thesaurus, Micromedex software and complementary manual analysis by pharmacist were used to identified DDIs. Clinical relevance of DDIs was scored using the validated scale of Hatoum. Results: A total of 91 patients were included, 15% of whom were participating in a clinical trial. Some imbalances were observed between patients from clinical trial and routine care (age, ECOG, MESPC/MCRPC). The median number of comedications used per patient was 6 [1-16]. Among real DDI, Enzalutamide was the anticancer agent with the higher risk of interaction (18-54% of patients). In modelized DDI, Enzalutamide and Apalutamide were the two most risky drugs (35-76% and 22-73% depending on Micromedex or Thesaurus analyze). Not all DDIs discovered were clinically significant according to Hatoum scale. Conclusions: DDIs are frequents, according to Micromedex and National Thesaurus tools but pharmacist and physician advices are essentials to determine their potential impacts.