bluuebunny/crossref_metadata_2025_split huggingface dataset:
Apalutamide toxicity and tolerability: A real-world multicentre experience in metastatic hormone-sensitive prostate cancer (MHSPC) in the United Kingdom (UK).
Authors: Ramamurthy Sindhu , Elumalai Thiraviyam , Pearson Rachel , Bolnykh Iakov , Muhammad-Afzal Tehreem , Olukiran Gbenro , Arora Ananya , Bradley Gay , Taft Kate , Lin Myint Nayan , Htike Ei The , Ince Will , Jiang Xue Yan 
Published: January 2024

107 Background: Apalutamide became available for mHSPC along with androgen deprivation treatment (ADT) in the UK in November 2021. We present here, to our best knowledge the first real world multicentre experience of Apalutamide use in mHSPC patients from three tertiary cancer centres from the UK. Our primary aim was to assess for toxicity and tolerability at this stage. Methods: We collected retrospective data from hospital prescription registries including all patients with mHSPC receiving Apalutamide between November 2021 and January 2023. Median period of follow up in our cohort was 14 months. Results: Two hundreds and ten patients received Apalutamide for mHSPC from three centres. The median age was 73 years. A total of 16.4% of the patients had recurrent mHSPC previously treated for localised PC and 83% were de novo metastatic. Of all patients, 43.3% had high-volume disease, and 56.7% had low-volume disease. The median presenting Prostate Specific Antigen (PSA) was 62 ng/l at diagnosis (range 0.87 to 5580). Undetectable PSA achieved in 43.3% of patient after starting Apalutamide and ADT. For those who have detectable PSA, median value was 0.22. Ninety percent of patients maintained their performance status (PS) at 0 or 1 on treatment. Most common side effects were fatigue (35.7%) and rash (11.4%). Cardiac adverse effects were recorded in 1.9% and thromboembolic events in 0.4%. Overall grade 3 and 4 toxicity was 5.2% across all symptoms assessed. To date, 83.3% patients continue on Apalutamide, 7.6 % discontinued due to toxicity and 9.1% had progressive disease (PD). Three deaths were recorded and all due to PD. Conclusions: In this multicentre retrospective analysis we found that Apalutamide and ADT is well tolerated in the real-world setting. Our patients are older and had lower volume metastasis compared with patients from the registry Trial (TITAN). Fatigue is more prevalent. Majority patients continue on Apalutamide with manageable side effects and good PS.
The frequency of use and enrollment impact of patient-centered outcomes in prostate cancer clinical trials.
Authors: Krischak Madison , Bank Merrick , Byrnes Mary , Stensland Kristian 
Published: January 2024

115 Background: Cancer treatments should help patients live either longer or better by improving patient quantity or quality of life. However, some trial endpoints do not correlate with overall survival, and are not noticeable to patients. Selecting endpoints for clinical trials that reflect these goals could improve the discovery process by ensuring trial results are of direct interest to patients, and perhaps by improving enrollment rates to trials. However, how frequently prostate cancer clinical trials use patient-centered outcomes, and how outcome type impacts trial enrollment, is unknown. Methods: On October 23, 2022, we queried ClinicalTrials.gov for full text records of phase 2-3 prostate cancer trials started after January 1, 2007. We extracted primary outcomes and other trial characteristics using a custom Python script. Two reviewers categorized each outcome into categories (e.g., overall survival, response rate, patient reported measure). As previously studied, the only valid surrogate for overall survival is metastasis-free survival. We considered these two outcomes or any outcome directly noticeable to a patient to be a patient-centered outcome. For completed or terminated trials, we defined ‘sufficient accrual’ as attaining 85% of a trial’s goal enrollment. We identified associations between trial outcome types and sufficient trial enrollment with chi-square tests and logistic regression. Results: Of 1,717 prostate cancer trials, only 37% used a patient-centered outcome, with 6% using overall or metastasis-free survival. Among 318 Phase 3 trials, 49% used a patient-centered outcome and 26% used overall or metastasis-free survival. Of 731 completed or terminated prostate cancer trials, 55% of trials and 68% of phase 3 trials reached sufficient enrollment (85% of enrollment goal). On multivariable analysis, trials with an overall survival endpoint had higher odds of sufficient enrollment (OR 8.0 [95% CI 2.2-33.5], p < 0.01), but trials with any patient-centered outcome had lower odds of sufficient enrollment (OR 0.25 [95% CI 0.11-0.54], p < 0.01). Conclusions: Less than half of prostate cancer trials use an outcome that is clearly patient-centered (i.e., affecting overall survival or an outcome noticeable to a patient). Further work is needed to clarify the use, understanding, and effect of outcome selection in cancer trials. Realigning trial efforts with patient-centered goals could improve the efficiency, productivity, and applicability of clinical trials.
Outcomes, frailty status, and body composition of men with hormone-sensitive prostate cancer treated with bicalutamide and dutasteride.
Authors: Lebenthal Justin M , Hahn Andrew Warren , Tidwell Rebecca , Zhang Krystal , Aparicio Ana 
Published: January 2024

122 Background: Prostate cancer is often a disease of the frail in which androgen withdrawal can further the risk of morbidity and mortality. This study aimed to describe a single institution experience with peripheral androgen blockade using bicalutamide and dutasteride (B+D) in men with hormone-sensitive prostate cancer (HSPC) in the context of body composition and frailty. Methods: Patients with HSPC treated with B+D at MD Anderson Cancer Center between 2010 and 2022 were retrospectively identified. Baseline and post-B+D frailty scores were calculated using the G8 geriatric score. Body composition was objectively measured from pre-treatment CT imaging. Differences in patient and disease characteristics between frail vs. not frail patients were compared with Kruskal Wallis tests or chi-square tests. Time on treatment (ToT), time to next treatment (TTnT) and overall survival (OS) were calculated by Kaplan-Meier methods, and comparisons by frailty status were made with the log rank test. Results: Forty-four patients were evaluable: median G8 frailty score was 13.5 with 22 patients classified as frail (G8 score ≤ 14) at baseline and after 6 months of B+D. ToT was shorter in frail individuals than non-frail (18.9 vs 38.2 months, p=0.03). TTNT was also shorter in frail individuals (20.9 vs 38.2 months, p=0.03). Only 3 patients have died, and 5-year OS is 81.3% for the entire cohort. Sarcopenia was found in 11 patients (52%) and sarcopenic obesity in 3 (14%). Conclusions: Bicalutamide and dutasteride was generally safe and feasible in a cohort of HSPC with increased pre-treatment frailty and sarcopenia. These findings suggest that peripheral androgen blockade is a eugonad treatment option that may warrant prospective study in at-risk populations and the application of frailty scores and measures of body composition can refine the relevant population. [Table: see text]
Dose modification in enzalutamide and abiraterone plus prednisolone for castration-resistant prostate cancer: Sub-analysis from ENABLE for PCa, a multicenter, randomized controlled trial.
Authors: Izumi Kouji , Mizokami Atsushi 
Published: January 2024

127 Background: Head-to-head comparison between enzalutamide (ENZ) and abiraterone plus prednisolone (ABI) demonstrated similar survival benefit for castration-resistant prostate cancer (CRPC) in ENABLE study for PCa. As it is previously reported that reduced dose of ENZ and ABI can maintain sufficient inhibitory ability of androgen receptor signaling, we analyzed the efficacy of modified dose in ENABLE study for PCa. Methods: ENABLE study for PCa is an investigator-initiated, multicenter, randomized controlled trial conducted in Japan. We analyzed survivals, prostate-specific antigen (PSA) response rate (≥50% decline from baseline), and safety assessment in patients treated with modified dose (ENZ ≤120 mg/day, ABI ≤750 mg/day) compared to those treated with standard dose (ENZ 160 mg/day, ABI 1000 mg/day) as a starting dose. Results: In total 92 patients in each arm treated and analyzed, the number of modified dose patients in the ENZ and the ABI arm was 16 and 16, respectively. Total 32 modified dose patients showed significantly better time to PSA progression (TTPP) and overall survival than 152 standard dose patients (HR 0.47, 95%CI 0.27-0.83, p=0.0379 and HR 0.35, 95%CI 0.19-0.63, p=0.0162). Although there was significantly longer TTPP in modified ABI group than standard ABI group (HR 0.29, 95%CI 0.14-0.62, p=0.0248), no significant difference was observed in TTPP between modified ENZ group and standard ENZ group (p=0.5366). There was significant difference in PSA response rate between modified ABI and standard ABI group (79% and 53%, respectively; P=0.0036). Similar adverse event rates and grades were observed in each treatment group. Conclusions: Modified ABI showed better outcomes than standard ABI and may be a potential treatment option for CRPC patients; however, all patients were of Japanese and patients in other countries were not included. Further study should be conducted including other ethnic backgrounds and focusing on different constitutions. Clinical trial information: UMIN000015529 .
Real-life data on [177Lu]Lu-PSMA-617: Descriptive analysis on the largest metastatic castration-resistant prostate cancer (mCRPC) cohort treated in France.
Authors: Roubaud Guilhem , Somme François , Barthelemy Philippe , Olivier Pierre , Massard Vincent , Giraudet Anne Laure , Flechon Aude , Girault Sylvie , Abadie Lacourtoisie Sophie , Bailly Clément , Viala Caroline , Godbert Yann 
Published: January 2024

129 Background: VISION study showed that [177Lu]Lu-PSMA-617 added to BSoC prolonged imaging-based progression-free survival and overall survival in patients (pts) with PSMA-positive mCRPC. French Health Authorities has granted a "cohort" early access for [177Lu]Lu-PSMA-617 in this indication. Methods: PSMA positive mCRPC pts pretreated with at least 1 taxane-based chemotherapy regimen and ≥1 androgen receptor pathway inhibitor (ARPI) were included. [177Lu]Lu-PSMA-617 (7.4 GBq) was administered up to 6 cycles every 6 weeks. Pts’ characteristics and safety data are described for the entire population. Efficacy was analyzed within a sub-population with 6 months follow-up min after 1st [177Lu]Lu-PSMA-617 injection. Adverse events (AE) grading was not evaluated. Results: From 12/1/2021 to 6/30/2023, 945 pts were included, and 535 pts were analyzed for efficacy. At data cut-off, 474 were still under treatment, and 471 stopped treatment due to disease progression (50.1%), AE (7.2%) or death (7.4%). 124 pts (26.3%) completed all 6 injections. Pts baseline characteristics: median age 73.2 (44-92) years; ECOG 0-1: 86.3%; median PSA level 70.9 (0.1 -6972) ng/ml; metastatic sites: bone 93.8%, lymph node 62.4%, liver 10.7%; previous taxane regimen: 97.1% of which 61.6% have received 2; prior ARPI treatment: 100% and 66.6% received 2 or more (median: 2). Concomitant treatment with ARPI was observed in 26.8%. In terms of efficacy results, the best imaging response was assessed by investigators (by RECIST 1.1 and PCWG3 on CT/bone scan and/or metabolic responses PET PSMA): 1.2% CR, 35.7% PR, 26.7% SD. 68.1% pts had a decrease in PSA level at any time point. Median time to PSA decrease was 1.22 (0.1–9.6) months. 12.8% (n= 121) of pts experienced >1 treatment-related (TR) AE, including 99 pts with ≥1 serious AE. 3 fatal cases related to treatment have been reported. The most reported TRAEs were thrombocytopenia (5.4% of pts) and anemia (5.0% of pts). Conclusions: In this large real-life cohort of mCRPC treated with [177Lu]Lu-PSMA-617 pts are heavily pretreated, received less concomitant ARPI treatment and higher incidence of 2 prior taxane regimens compared to VISION study. Safety profile of [177Lu]Lu-PSMA-617 remains favorable. Since the cohort is still ongoing, updated results will be presented at ASCO GU congress, including longer follow-up period and higher number of pts who completed treatment.
ARTO trial: Overall survival analysis from a randomized phase II trial testing the benefit of adding stereotactic body radiotherapy to abiraterone acetate in patients with oligometastatic castrate-resistant prostate cancer.
Authors: Francolini Giulio , Di Cataldo Vanessa , Garlatti Pietro , Detti Beatrice , Caini Saverio , Bruni Alessio , Ingrosso Gianluca , D'Angelillo Rolando Maria , Alitto Anna Rita , Augugliaro Matteo , Triggiani Luca , Parisi Silvana , Facchini Gaetano , Banini Marco , Simontacchi Gabriele , Desideri Isacco , Meattini Icro , Valicenti Richard K. , Livi Lorenzo 
Published: January 2024

132 Background: ARTO (NCT03449719) is a multicentre, randomized phase II trial testing the benefit of stereotactic body radiation therapy (SBRT) addition to abiraterone acetate (AA) in oligometastatic Castrate Resistant Prostate Cancer (CRPC) patients. Trial ended in October 2022. Results already showed significant benefit in terms of biochemical response and Progression Free Survival (PFS) in the experimental arm, the trial was positive for its primary endpoint. Here we present an updated overall survival (OS) analysis. Methods: Patients affected by oligometastatic CRPC (< 3 non-visceral metastatic lesions) were enrolled in the trial and randomized 1:1 to receive either AA alone (control arm) or associated with concomitant SBRT on all sites of disease (treatment arm). Kaplan-Meier survival analysis was performed to compare OS in the different arms of treatment. Results: One hundred fifty-seven patients were enrolled in ARTO trial. After a median follow up of 27 months, 29 patients died (9 vs 20 in the experimental vs control arm, respectively). Median OS was not reached in neither of the two arms of treatment, with a non-significant trend in favour of the experimental arm (p=0.07). Conclusions: After an updated follow up analysis, results confirmed good prognosis for this population of oligo-metastatic CRPC patients. First line abiraterone acetate conferred long term OS in a selected cohort of patients affected by oligometastatic disease. A positive, nonsignificant trend was found in favour of experimental arm. Considering the low number of events detected, longer follow up is needed to explore impact of upfront SBRT on OS within this randomized phase II trial. Clinical trial information: NCT03449719 .
Association of initial adjustment dose of apalutamide with progression to castration-resistant prostate cancer and skin-adverse events in men with metastatic castration-sensitive prostate cancer: A multicenter retrospective study of CsJUC cohort.
Authors: Tohi Yoichiro , Kato Takuma , Kobayashi Keita , Daizumoto Kei , Fukuhara Hideo , Ohira Shin , Katayama Satoshi , Shimizu Ryutaro , Takamoto Atsushi , Nishimura Kenichi , Ikeda Kenichiro , Nagami Taichi , Sugimoto Mikio ,   Chu-shikoku Japan Urological Consortium
Published: January 2024

137 Background: Japanese patients with prostate cancer (PC) treated with apalutamide often encounter skin-adverse events (AE), which might lead to adjust the initial-dose of apalutamide. However, concerns have emerged regarding the potential impact of these dose adjustments on the overall efficacy of apalutamide in real-world clinical practice. We aimed to evaluate the association between adjustment of apalutamide dose and clinical outcome in Japanese men with metastatic castration-sensitive PC (mCSPC). Methods: We retrospectively evaluated 108 mCSPC patients treated with apalutamide. We divided patients into two groups: initial full-dose and reduced-dose recipients. The primary outcome was the impact of apalutamide dose adjustment on progression to castration-resistant prostate cancer (CRPC) and PSA response. The secondary outcomes were the impact of apalutamide dose adjustment on the incidence of the skin-AE. Results: Initial reduced-dose recipients of apalutamide were observed in 16.7%. There were no differences in cancer characteristics, such as CHAARTED criteria between the groups. Initial full-dose recipients were significantly associated with a longer time to CRPC than initial reduced-dose recipients [median NA (NA - NA) vs. 19 months (95% CI, 10 - NA), P=0.0161], although the percentages of the initial full-dose recipients who reduced apalutamide dose were 30%, 44.4%, 60%, and 63.3% at 3, 6, 9, and 12 months, respectively. The percentage of PSA <0.2 decline at 3 months did not differ between the groups (59.1% vs 50%, P=0.602), but overall PSA 90% decline was higher in the initial full-dose recipients (88.8% vs 66.7%, P=0.027). Skin-AE occurred 50% in initial reduced-dose recipients and 51.1% in initial full-dose recipients, with no difference between the groups (P>0.999). Furthermore, time to skin-AE was not different between the groups (74 days vs. 69 days, P=0.992). Conclusions: Our study suggested the potential negative implications of initial apalutamide dose adjustments on clinical outcomes in Japanese men with mCSPC.
Real-world effects of novel androgen receptor axis-targeted agents on oncological outcomes in non-metastatic castration-resistant prostate cancer: A multi-institutional retrospective study.
Authors: Fujita Naoki , Hatakeyama Shingo , Tabata Ryuji , Yoneyama Takahiro , Hashimoto Yasuhiro , Sato Satoshi , Ohyama Chikara 
Published: January 2024

142 Background: The benefits of novel androgen receptor axis-targeted agents (ARATs) on oncological outcomes in patients with non-metastatic castration-resistant prostate cancer (nmCRPC) in real-world settings are unclear. Methods: This multi-institutional retrospective study included 178 patients with nmCRPC treated between September 2003 and August 2022. Patients were divided into two groups: those who were treated with any novel ARATs, including apalutamide, enzalutamide, darolutamide, and abiraterone acetate, during any line of nmCRPC treatment (novel ARATs group) and those who were not (control group). Multivariable Cox proportional hazards regression analyses were performed to evaluate the effects of novel ARATs on metastasis-free survival (MFS) and overall survival (OS). Results: The median age and follow-up period after nmCRPC diagnosis were 76 years and 37 months, respectively. Of the 178 patients, 122 (69%) were treated with novel ARATs after nmCRPC diagnosis. The MFS and OS in the novel ARATs group were significantly longer than those in the control group ( P < 0.001 and P = 0.020, respectively). In multivariable analyses, a prostate-specific antigen doubling time (PSADT) of < 3 months and novel ARATs were independently and significantly associated with MFS and OS (Table). The effects of novel ARATs on MFS were consistently observed across subgroups stratified by age (< 75 years or ≥ 75 years), history of radical treatment (no or yes), biopsy Gleason score (< 9 or ≥ 9), clinical stage (≤ cT3 and cN0, or cT4 or cN1), and PSADT (≥ 3 months or < 3 months). Conclusions: Novel ARATs were significantly associated with improved oncological outcomes in patients with nmCRPC in a real-world setting, regardless of tumor aggressiveness. [Table: see text]
Characteristics and outcomes of patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) treated with lutetium-177–PSMA-617 (PSMA-RLT) in a real-world setting.
Authors: Kersting David , Kim Moon-Sung , Puellen Lukas , Seidl-Rathkopf Kathi , Schinwald Nicole , Mpofu Philani , Altomare Ivy , Sujenthiran Arun , Royce Trevor Joseph , Buhl Christoph , Grünwald Viktor , Herrmann Ken , Kleesiek Jens , Hadaschik Boris A. 
Published: January 2024

143 Background: The VISION trial demonstrated a survival benefit of PSMA-RLT treatment (tx) for pts with PSMA-positive mCRPC. However, outcomes in a real-world setting are unknown. PSMA-RLT has been used at Essen University Hospital (UKE) in Germany since 2017. This retrospective cohort study describes characteristics and real-world overall survival (rwOS) of pts with mCRPC treated with PSMA-RLT. We contextualize these findings with results from a US-based mCRPC cohort that did not receive this novel tx. Methods: The UKE cohort included mCRPC pts treated with ≥ 1 cycle of PSMA-RLT from 11/2017 to 10/2022. Data comprised structured and unstructured data from UKE’s electronic health record (EHR). The US cohort was selected from the nationwide EHR-derived Flatiron Health database. It included pts with mCRPC diagnosis (dx) from 01/2014 to 09/2021 who received tx (=index tx) following ≥ 1 taxane and ≥ 1 androgen receptor pathway inhibitor (ARPI). Results: In the UKE cohort (N = 219, median (med) age: 73, interquartile range (IQR): 67, 78) med time from initial dx and mCRPC dx to the initiation of PSMA-RLT was 69 mos (IQR: 42, 128) and 23 mos (IQR: 13, 40), respectively. Pts were heavily pre-treated (1 taxane: 55.5%, ≥ 2 taxanes: 27.8%; 1 ARPI: 37.3 %, ≥ 2 ARPIs: 58.9%). Disease burden at the time of tx start was extensive, as indicated by sites of metastases (for tumor patterns see table). Median OS (mOS) from the start of PSMA-RLT was 9.8 mos (95% CI: 8.6, 11.3). In the US cohort (N = 857, med age = 71, IQR: 65, 78) med time from initial dx and mCRPC dx to index tx was 49 mos (IQR: 27, 99) and 16 mos (IQR: 10, 25), respectively. 88.9% of pts received prior tx with 1 taxane and 11.1% with ≥2 taxanes, 65% with 1 ARPI and 35% with ≥ 2 ARPIs. Med OS for US patients was 8.5 mos (95% CI:7.6, 9.1). Conclusions: This study provided the unique opportunity to describe real-world outcomes for late stage mCRPC patients treated with PSMA-RLT. The study design did not allow for a direct comparison between the two cohorts. Qualitatively, UKE patients were heavily pre-treated with extensive disease burden at the start of PSMA-RLT. Nevertheless, the study demonstrated promising rw outcomes for patients with mCRPC under PSMA-RLT. Future work, including the direct comparison of PSMA-RLT versus other tx in a similar disease setting, will help further characterize the benefit of this novel tx in practice. [Table: see text]