bluuebunny/crossref_metadata_2025_split huggingface dataset:
Practice patterns and predictors of treatment intensification in patients with metastatic castration-sensitive prostate cancer.
Authors: Gotto Geoffrey T. , Yip Steven M. , Shayegan Bobby , O'Sullivan Dylan E. , Wallis Christopher J.D. , Basappa Naveen S. , Cagiannos Ilias , Hamilton Robert James , Ferrario Cristiano , Fernandes Ricardo , Danielson Brita , Saad Fred , Hotte Sebastien J. , Brenner Darren R. , Cheung Winson Y. , Boyne Devon J. , Chan Katherine , Osborne Brendan , Zardan Anousheh , Malone Shawn 
Published: March 2023

76 Background: In recent years, treatment intensification beyond androgen deprivation therapy (ADT) with several novel therapies have shown survival benefit in patients with metastatic castration-sensitive prostate cancer (mCSPC). Given the rapidly evolving landscape in mCSPC treatment, there is a need to better understand how treatment strategies fit in real-world clinical practice and are combined/sequenced with other available therapies. Methods: Using electronic medical records and administrative data, a population-based retrospective cohort study was conducted. Patients aged ≥18 years of age who were newly diagnosed with de novo mCSPC and initiated ADT post-diagnosis between 2010 to 2020 in Alberta, Canada, were included. Treatment intensification was defined as the receipt of apalutamide, abiraterone acetate, enzalutamide, or chemotherapy (e.g. docetaxel) within 180 days of ADT initiation. Results: A total of 2,515 de novo mCSPC were identified during study period with 2,098 (83%) patients initiating ADT post-diagnosis. Of those, 525 (25%) received intensification beyond ADT. The percentage of patients who were intensified was 3% in 2010-2013 and gradually increased to 67% in 2020. Between 2014-2017, docetaxel was the most common therapy for intensification, but its use decreased considerably in 2018-2020 with abiraterone acetate, apalutamide and enzalutamide becoming increasingly available in the mCSPC setting. Upon progression, 46% and 22% in the intensified group versus 38% and 13% in the ADT-alone group initiated one and two-lines of subsequent therapies respectively. Abiraterone acetate and enzalutamide were the most common subsequent therapy for both the intensified (32% and 31% respectively) and the ADT-alone (56% and 38% respectively) groups. Docetaxel (24%) was used as subsequent therapy among mCSPC patients who were intensified with oral systemic agents. In multivariable logistic regression analyses of patients diagnosed in 2014-2020, significant predictors of intensification were younger age at diagnosis, lower Charlson comorbidity index, greater number of metastatic sites, shorter time to ADT initiation, referral to a specialists/cancer centres, surgery or radiation prior to ADT, and more recent year of diagnosis (all p<0.05). Conclusions: In Alberta, Canada, there has been a considerable increase in the utilization of ADT intensification therapies that correspond with the timing of clinical trial data and approvals of novel agents. Early referral to specialists/cancer centres is warranted to intensify mCSPC treatment beyond ADT and to improve patients’ outcomes. [Table: see text]
Management disparities in metastatic castrate-sensitive prostate cancer (mCSPC).
Authors: Mar Nataliya , Kaakour Dalia 
Published: March 2023

79 Background: Recent approvals in management of high-volume mCSPC offer major improvements in patient outcomes. Triplet therapy combining androgen deprivation therapy (ADT) with docetaxel (D) and novel hormonal therapy (NHT) is the new standard of care in this patient population. Patients ineligible for triplet therapy should receive doublet therapy with ADT plus D or NHT based on category 1 evidence. Multiple retrospective datasets examining the “real-world” mCSPC treatment landscape note significant underutilization of therapies beyond ADT and discordance with treatment guidelines. Methods: A 15-question survey to assess management patterns was electronically distributed to various mCSPC providers in California and Washington. Results: A total of 40 responses were received, with 62.5% identifying as medical oncologists (MO), 20.0% as urologists, 5.0% as radiation oncologists, and 12.5% as advanced practitioners/other. Out of physician responders, 48.6% were academic and 51.4% were community-based. When treating newly diagnosed fit mCSPC patients, 20.0% would prescribe triplet therapy, 42.5% ADT/NHT, 5.0% ADT/D, 5.0% ADT/bicalutamide, 0% ADT alone, 10.0% other therapies, and 17.5% would refer out for therapies beyond ADT. When comparing academic versus community oncologists, 66.7% versus 0% would prescribe triplet therapy, while 22.2% versus 68.8% would prescribe ADT/NHT. Some perceived barriers to following mCSPC treatment guidelines included difficulty keeping up with rapidly evolving data/too many treatment options in 27.5%, insurance coverage concerns in 22.5%, difficulty obtaining early referrals for these therapies in 12.5%, patient factors in 10.0%, and toxicity concerns in 2.5%. When making referrals to MO, 37.5% of non-MO responders would do so at development of mCSPC and 6.3% at mCRPC. Conversely, 24.2% of MO perceived receiving referrals at development of mCSPC and 33.3% at mCRPC. Patterns of ordering genomic testing are listed, with biggest perceived barriers being cost, inadequate access to sequencing platforms and genetic counselors, lack of confidence in counseling about results, and patient refusal. Upon progression from mCSPC to mCRPC, ordering of repeat tumor biopsies would occur “sometimes” by 40.0% of providers, “rarely” by 20.0%, and “never” by 20.0%. Conclusions: Multiple provider disparities when managing mCSPC patients still exist. Our survey demonstrated higher compliance with treatment guidelines than in previous retrospective datasets, possibly due to higher proportion of academic providers. Increased provider awareness of genomic testing recommendations is also needed. [Table: see text]
Association of intermittent vs continuous androgen deprivation therapy with cardiovascular disease and endocrine/metabolic disorders in patients with metastatic prostate cancer.
Authors: Morgans Alicia K. , Ebrahimi Ramin , Bobbili Priyanka J. , Nwokeji Esmond , Gandhi Raj , Desai Raj , Horvath Krisztina , Ryan Michael , Hanson Sarah , Duh Mei Sheng , Preston Mark A. 
Published: March 2023

82 Background: There is mixed evidence on the risks of cardiovascular disease (CVD) and endocrine/metabolic disorders associated with long-term intermittent and continuous androgen deprivation therapy (iADT and cADT, respectively) for metastatic prostate cancer (mPC). This study examined these risks in patients (pts) with mPC receiving iADT vs cADT in the US. Methods: This was a retrospective cohort study of SEER-Medicare pts with mPC initiating ADT (2010–2017), with ≥36 months of continuous insurance coverage, unless death occurred, who did not receive chemotherapy or a second-generation anti-androgen during follow-up. iADT and cADT cohorts were defined by treatment patterns and gaps in therapy. Comorbidities and clinical events were identified using ICD-9/10-CM codes. Outcomes examined were major adverse cardiovascular events (MACE [myocardial infarction (MI), stroke, cardiomyopathy/heart failure (HF), pulmonary embolism (PE), ischemic heart disease (IHD), or all-cause mortality]) and endocrine/metabolic events (diabetes, hypercholesterolemia, bone fractures, or osteoporosis). Inverse probability of treatment weighting (IPTW) was used to adjust for differences between cohorts; weighted Cox models were used to estimate the hazard ratio (HR) of the outcomes. Subgroup analyses examined pts by CVD history; a sensitivity analysis was performed restricting the definition of MACE to include CVD-related mortality as a component, i.e., MACESA (MI, stroke, cardiomyopathy/HF, PE, IHD, or CVD-related mortality). Results: 2234 pts with mPC were included; 478 (21%) received iADT and 1756 (79%) cADT. Median follow-up time was 27 and 13 months, and time on ADT (excluding gaps for iADT pts) was 24 and 19 months for the iADT and cADT cohorts, respectively. Deaths occurred in 39% of iADT pts vs 55% of cADT pts; PC was the most common cause of death in both cohorts. In adjusted analyses, pts receiving cADT had a higher risk of MACE vs iADT. No differences in risk of endocrine/metabolic events were observed. Subgroup analysis showed that baseline history of CVD did not alter the results for MACE. Sensitivity analysis results showed no difference in risk of MACESA between pts receiving cADT vs iADT. Conclusions: Pts with mPC receiving cADT had a higher risk of MACE (including all-cause mortality), and no difference in risk of endocrine/metabolic events, compared with those receiving iADT. When MACE was restricted to include CVD-related mortality, there was no difference in risk between cohorts. [Table: see text]
Multicenter population-level analysis of systemic therapy use in metastatic or recurrent prostate cancer.
Authors: Mohamed Heba , Kim Grace , Macphail Corin , Bhuiyan Ishmam , Sidhu Taylor , Emami Amir , Huang Longlong , Sun Shaun Zheng , Tyldesley Scott , Ko Jenny J. 
Published: March 2023

89 Background: Treatment (tx) options for metastatic prostate cancer (mPC) have advanced significantly. There is a need for data in prescribing patterns and real-world survival outcomes of new therapeutics. Methods: We conducted chart review on all consecutive patients (pts) diagnosed with any stage of PC between 2016-2017 in British Columbia, and only included pts with de novo metastasis or later recurrence. We performed descriptive statistics, univariate and multivariate analysis to examine overall survival (OS). Results: This study included 796 pts with either de novo metastatic (n=554, 69.6%) or recurrent PC (N=242; 30.4 %); 743 (93.3%) had metastasis by time of cutoff (Sep 1, 2022). Median age at diagnosis of mPC in all patients was 73 (range 45-98). 790 (99.2%) started ADT. 263 (35.4%) had additional line of tx started with ADT at mCSPC; 309 (38.8%) had 1st line tx started at mCRPC. 149 pts (18.7%) had testing for homologous repair defects (21 positive). Radiotherapy (RT) to prostate for mPC were given to 93 (11.6%). 307 (38.6%) received 1 line of tx; 181 (22.7%), 2; 128 (16.1%), 3 or more. 432 (54.3%) received >=1 androgen receptor-axis-targeted therapies (ARAT). At cutoff, 474 (59.5%) died; most (n=400; 84.4%) died of prostate cancer. Pts who only stayed on ADT or who stayed on 1 additional tx had better OS than who had more than 1 line (NR vs. 55.5m vs. 21.0m, p=0.03). Similarly, pts who required no ARAT or stayed on 1 ARAT had longer OS than patients who had more than 1 ARAT (NR vs. 48.5m vs. 22.5m, p=0.009). No statistical difference in OS was seen between pts who had chemotx vs none, or pts on trial vs none. None of age, PSA at metastatsis, Gleason score, ADT type, RT to prostate or number of systemic tx were identified as an independent factor affecting OS on multivariate analysis. Pts with comorbidities (hypertension, CHF, diabetes, seizure, prior stroke, CAD or dementia) received abiraterone/prednisone, enzalutamide or apalutamide at a similar rate. Conclusions: Our multicenter data show low uptake of early treatment intensification in pts with mPC. Similar to other real-world data to date, pts who required less switch to another systemic tx were associated with better OS. Different ARATs were prescribed despite potential side effects at a similar rate to pts with major comorbidities.
Neoadjuvant platinum-based chemotherapy for clinically node-positive penile squamous cell carcinoma: An international, multicenter, real-world study.
Authors: Rose Kyle M. , Sanchez Darren , Mustasam Arfa , Sandstrom Reagan , Marchetti Kathryn , Zacharias Niki Marie , Pagliaro Lance C. , Alifrangis Constantine , Moses Kelvin A. , Albersen Maarten , Roussel Eduard , Master Viraj A. , Nazha Bassel , Zhuang Tony , Montgomery Jeffrey S. , Protzel Chris , Machado Marcos Tobias , Spiess Philippe E. , Pettaway Curtis Alvin , Chahoud Jad 
Published: March 2023

9 Background: The efficacy of neoadjuvant platinum-based chemotherapy (NAPC) in penile squamous cell carcinoma (PSCC) was provided by small clinical trials, leaving clinicians with scant evidence-based guidance. Thus, we aimed to analyze real-world outcomes of patients with PSCC who received NAPC prior to surgical resection. Methods: Patients from 9 tertiary care centers who had undergone NAPC prior surgical resection for PSCC were included with locally advanced (cTany, cN+), non-metastatic (M0) disease. The primary and secondary outcomes were overall survival (OS) and progression-free survival (PFS), Response was determined via best overall response measured with RECIST 1.1 criteria. Results: 167 patients were included, 137 (84%), of which received TIP prior to surgical resection. Ninety-two (55%) patients died during follow up, and the mean follow up for survivors was 57 months. The median OS was 42 months, while the median PFS was 17 months. The table details the response rates to NAPC, the associated survival, and Cox Proportional Hazards Modelling of OS and PFS. Predictors for OS and RFS included lymphovascular invasion, positive number of lymph nodes, extranodal extension, downstaging, best overall response, and ypN status. Figure 1 demonstrates OS outcomes by RECIST best response after chemotherapy, presence of downstaging after NAPC, ypN stage, and presence of extranodal extension. Conclusions: Upfront NAPC is effective in patients with lymph node metastases from penile carcinoma. Unsurprisingly, patients who demonstrated a robust response to therapy had improved survival outcomes compared to those who had not—as measured by RECIST criteria, tumor downstaging, pN staging, and presence of extranodal extension. This study represents the largest conglomeration of multi-institutional penile carcinoma patients treated with NAPC, and provides further supportive data for multimodal therapy for advanced penile cancer patients while prospective clinical trials complete accrual. [Table: see text]
Radium-223 for mCRPC, a real-world experience study from 7 Galician medical centers.
Authors: Anido Herranz Urbano , Fernandez Calvo Ovidio , Martinez Breijo Sara , Fernández Núñez Natalia , Nogareda Seoane Zulema , Garrido Pumar Miguel , Casas Javier , Muñiz Garcia Gloria , Portela Pereira Paula , Gomez Caamaño Antonio , Pérez Fentes Daniel , Santomé Lucía , Huidobro Vence Gerardo , Molina Díaz Aurea , Medina Ana , Ruiz Bañobre Juan , Vázquez Estévez Sergio 
Published: March 2023

96 Background: Radium-223 represents an option for symptomatic metastatic castration-resistant prostate cancer (mCRPC) after demonstrated an overall survival improvement in the ALSYMPCA trial. Radium-223 real-life experiences are scarce, particularly after the results of the ERA-223 trial. To describe Radium-223 outcomes in real life practice, and specifically those related with bone health, sequence of treatment, and prognostic factors. Methods: Multicenter retrospective study of a cohort of 143 patients with mCRPC treated with Radium-223 in either the second line or third line of therapy or beyond in the context of routine clinical practice between 11 March 2013 and 26 July 2022, in seven Galician hospitals. Survival estimates were calculated by the Kaplan-Meier method, and groups were compared with the log-rank test. The Cox proportional hazards regression model was used to evaluate factors independently associated with OS. Between March 11, 2013, and July 26, 2022, 143 patients were enrolled from 5 Galician hospitals. With a median follow-up of 9.68 months. All patients signed an informed consent form agreeing to participate in this observational study, that was approved by the Galician Ethics Committee, registration code 2018/282. Results: Baseline patient and disease characteristics are summarized. Median follow-up was 9.68 months. Median overall survival (OS) was 12 months (95% CI 9.7 – 16.0). Best OS outcomes were achieved in second and third line, 18 months (95% CI 12.0 – 26.0) and 9.4 months (95% CI 8.0 – 12.0) months, respectively. Among those baseline clinic-analytical factors analyzed, only alkaline phosphatase level >354 UI/L was correlated with a worse OS (HR 2.56 (95% CI 1.39 – 4.72; p=0.003) and the number of cycles of Radium-223 received (HR 0.63 (95% CI 0.54 – 0.73; p<0.001) were prognostic factors for Radium-223. Importantly, ninety-nine of patients (80%) were treated with bone-targeted therapy for bone metastases with no OS differences (p=0.66). Conclusions: In our study, Radium-223 efficacy was consistent with previously reported. Best efficacy was achieved in the second or third line of therapy, independently of docetaxel use. Patients with high baseline alkaline phosphatase had worse OS. Few patients presented skeletal-related events, which could be explained by an adequate use of bone-targeted therapy (zoledronic acid or denosumab). [Table: see text]
Real world (rw) homologous recombination repair (HRR) gene mutation testing trends in patients (pts) with metastatic castrate-resistant prostate cancer (mCRPC) in the United States (US).
Authors: Barata Pedro C. , Montgomery Rachel , Last Matthew , Gillespie-Akar Liane , Nazari Jonathan , Arondekar Bhakti , Niyazov Alexander 
Published: March 2023

98 Background: Previous research suggests that HRR mutations may have prognostic value in mCRPC. Additionally, HRR mutations are therapeutically relevant and can inform treatment decisions. Limited information is available on HRR mutation testing rates in the US. This study assessed rw HRR testing patterns in pts with mCRPC in the US and described characteristics associated with HRR testing. Methods: Retrospective data from pts with mCRPC initiating first line (1L) treatment between 2014 – 2021 was obtained from the nationwide Flatiron Health electronic health record-derived de-identified database. Pt demographic and clinical characteristics were summarized descriptively across subgroups by HRR gene testing status (tested vs not tested). A multivariable logistic regression model was used to assess factors associated with receiving HRR testing, and included covariates for demographic, clinical, and treatment characteristics. Results: A total of n=8,166 pts with mCRPC receiving 1L treatment were identified. The mean age of the cohort was 72.9 (standard deviation (SD) 8.1) years. Overall, 2,122/8,166 (26%) were known to have received HRR mutation testing. Pts who did not receive HRR testing were older compared to HRR tested pts (mean age 73.7 (SD 8.5) vs 70.6 (SD 7.5) years). A higher proportion of HRR tested were receiving treatments from an academic medical center vs community practice (14.5% vs. 7.7%). Multivariable logistic regression indicated age > 65 (vs < 65 years), Black race (vs White), being treated in the community (vs academic), and having de novo metastatic disease (vs recurrent) were associated with a statistically significant lower odds of HRR mutation testing. In contrast, a higher socioeconomic status and being diagnosed with mCRPC after 2018 were associated with a statistically significant increased odds of HRR mutation testing. Conclusions: In this rw study, a minority of US pts with mCRPC received HRR mutation testing. Disparities in HRR mutation testing exist, and focused efforts to increase HRR testing should be developed, especially among Black pts, pts with lower socioeconomic status, pts treated in the community setting, and pts > 65 years of age. [Table: see text]
CYCLONE 3: A phase 3, randomized, double-blind, placebo-controlled study of abemaciclib in combination with abiraterone plus prednisone in men with high-risk, metastatic, hormone-sensitive prostate cancer (mHSPC).
Authors: Smith Matthew Raymond , Matsubara Nobuaki , McKay Rana R. , Piulats Josep M. , Todenhöfer Tilman , Zhang Tian , Fasnacht Nicolas , Sherwood Sarah , Johnston Erica L. , Schaverien Clare , Lithio Andrew , Nacerddine Karim , Agarwal Neeraj 
Published: March 2023

TPS289 Background: Landmark trials have established a survival benefit for novel hormonal agents (NHA) added to androgen deprivation therapy (ADT) for mHSPC. Yet, there is a significant medical need to expand therapeutic options, especially for pts with high-risk mHSPC who experience poorer outcomes. Abemaciclib is an oral selective inhibitor of cyclin-dependent kinase 4 and 6 (CDK4 & 6) dosed on a continuous schedule, approved for the treatment of node-positive high-risk early-stage and advanced or metastatic HR+, HER2- breast cancer. Analogous to the estrogen receptor signaling pathway in breast cancer, there is evidence that the androgen receptor axis activates CDK4 & 6 to sustain prostate cancer cell proliferation, and upregulation of cyclin D1 is a potential mechanism of resistance to NHA therapy. In preclinical models, abemaciclib induces cell cycle arrest and inhibition of prostate tumor growth. Methods: CYCLONE 3 (NCT05288166) is a global, randomized, double-blind, placebo-controlled study evaluating the addition of abemaciclib to abiraterone+prednisone (AP) in pts with high-risk mHSPC. Approximately 900 pts with high-risk mHSPC defined by ≥4 bone metastasis and/or visceral disease will be randomised in a 1:1 ratio to the AP + abemaciclib or AP + placebo arm. Up to 3 months of ADT prior to randomization is permitted; prior D for mHSPC will be excluded per planned protocol amendment. Pts who have not undergone orchiectomy will continue ADT. Stratification factors are de novo mHSPC and visceral metastases. Primary endpoint is investigator-assessed radiographic progression-free survival (rPFS). Key secondary endpoints include rPFS assessed by blinded independent central review, castration-resistant prostate cancer-free survival, overall survival, time to pain progression, safety and pharmacokinetics. Enrollment is open at approximately 270 sites across 25 countries. Clinical trial information: NCT05288166 .