bluuebunny/crossref_metadata_2025_split huggingface dataset:
Electronic patient reporting outcomes are a promising predictive factor of prostate cancer patient survival: The Protecty study.
Authors: Helissey Carole , Riviere Clémentine , Becheriat Selma , Vanquaethem Hélène , Parnot Charles , Brureau Laurent 
Published: February 2022

76 Background: The benefits of Electronic Patient Remote Outcomes (e-PRO) for telemonitoring are well established, allowing early detection of illnesses and continuous monitoring of patients. We have previously shown high levels of compliance of use of telemonitoring in daily care. This new PROTECTY study assesses the predictive power of patient health status in the first month of treatment on survival, evaluated with the telemonitoring platform Cureety. Methods: This prospective study was conducted at the Military Hospital Bégin on prostate cancer patients. Patients were allowed to respond to a symptomatology questionnaire based on CTCAE v.5.0, personalized to their pathology and treatment. An algorithm evaluates the health status of the patient based on the reported adverse events, with a classification into 2 different states: Good Health status (A) Poor Health status (B) In case of A, the patient received therapeutic advice to help manage each of the reported adverse events. In case of B, the patient is invited to call the hospital. For the purpose of this analysis, we collected their health status during the first month after initiation of treatment. The primary endpoint was to assess if the first month health status is a predictive factor of progression free-survival (PFS) for prostate cancer patient. The secondary endpoint was to assess if the first month health status is a predictive factor of overall survival (OS) for prostate cancer patient. Results: Sixty-one patients were enrolled between July 1st, 2020 and June 30st, 2021. The median age was 74.0 (range 58.0 – 94.0). 62% presented a metastatic stage, and the most represented cancer was mHSPC with 39,5% among metastatic patients. Overall, 2443 questionnaires were completed by the patients, 4.0% resulted in a health classification in state B. 86,9% of patient were classified in group A the first month. 13,1% of patient were classified in group B the first month. The median follow up was 12.3 months. PFS at 12 months was 89% in A group vs 60% in B group, p=0,17 OS at 12 months was 100% in A group vs 86% in B group, p=0,15. Conclusions: Our study is the first to assess the impact of tolerance treatment on survival. The initial results suggest that e-PRO assessment by the platform could help identify in the early stages the patients that require further health assessment and potential therapeutic changes. While further follow-up of more patients will be required, our study highlights the importance of e-PRO in cancer patient care.
A prospective study of the relationship between CRPC patient’s quality of life after enzalutamide and serum testosterone levels measured via LC-MS/MS.
Authors: Miyazawa Yoshiyuki , Nakamura Toshiyuki , Takezawa Yutaka , Shimizu Nobuaki , Matsuo Yasushige , Ogura Haruyuki , Takei Tomoyuki , Arai Seiji , Sekine Yoshitaka , Suzuki Kazuhiro 
Published: February 2022

79 Background: Enzalutamide (ENZ) is used to treat patients with castration-resistant prostate cancer (CRPC). Quality of life (QOL) during ENZ treatment for CRPC patients is very important, but the markers that predict QOL are unknown. We investigated the relationship between serum testosterone (T) levels before ENZ and QOL changes in CRPC patients. Methods: We conducted a prospective study from 2014 to 2018 at Gunma University Hospital and related facilities. We analyzed 95 patients who were able to evaluate QOL by FACT-P before, 4 weeks, and 12 weeks after ENZ administration. We measured serum T levels using liquid chromatography-tandem mass spectrometry (LC-MS/MS). This study was approved by the institutional review board of Gunma University Hospital (No.1177). Results: The study population of 95 patients had a median age of 72 years and median PSA of 21.6 ng/ml. The median overall survival from the time of ENZ administration in 95 cases was 26.8 months. The median serum T levels before ENZ treatment was 50.0 pg/ml. The mean total FACT-P score before ENZ administration, 4 weeks and 12 weeks later were 95.8, 91.7, and 90.1, respectively. 95 patients were divided into two groups, a high T levels (T-High) group and a low T (Low-T) group, and changes in FACT-P were examined. The mean FCAT-P values in the High-T and Low-T groups were 98.5 and 84.6 after 4 weeks and 96.4 and 82.2 after 12 weeks, which were significantly higher in the High-T group (p < 0.05, respectively). In the Low-T group, the mean FACT-P value after 12 weeks was significantly lower than that before administration (p < 0.05). Conclusions: It was suggested that the serum T levels of CRPC patients before ENZ treatment may be useful for predicting marker of QOL changes after ENZ treatment.
Exposure-adjusted safety analyses of the VISION phase 3 trial of 177Lu-PSMA-617 in patients with metastatic castration-resistant prostate cancer.
Authors: Chi Kim N. , Adra Nabil , Garje Rohan , Michalski Jeff M. , Lavalaye Jules , Kempel Mette Moe , Brackman Marcia , Perraud Kevin , Holder Geoffrey , Armstrong Andrew J. 
Published: February 2022

85 Background: In the VISION trial, targeted radioligand therapy with 177Lu-PSMA-617 significantly prolonged radiographic progression free survival (rPFS) and overall survival when added to standard of care (SoC) in patients with advanced prostate-specific membrane antigen (PSMA)-PET-positive metastatic castration-resistant prostate cancer. There was a higher incidence of treatment-emergent adverse events (TEAEs) with 177Lu-PSMA-617 + SoC vs SoC. However, treatment exposure was more than three times longer in the 177Lu-PSMA-617 + SoC arm and thus relative toxicity may have been overestimated. A post hoc analysis of the relationship between exposure and frequency of TEAEs was performed to facilitate comparison of rates between arms. Methods: In this international, open-label study, adult patients previously treated with ≥ 1 androgen receptor pathway inhibitors and 1–2 taxane regimens were randomized 2:1 to 177Lu-PSMA-617 (7.4 GBq Q6W, ≤ 6 cycles) + SoC or SoC. Safety was a secondary endpoint. TEAEs (regardless of causality) were reported from start of randomized treatment for up to 30 days after last treatment administration (including SoC) or 1 day before subsequent anticancer treatment, whichever occurred first. Overall TEAE incidence was adjusted for treatment exposure by calculating incidence per 100 patient treatment-years (PTY). The analysis was performed for the first occurrence of TEAEs. Results: Exposure-adjusted incidence of any grade, grade ≥ 3 and selected TEAEs are listed in the table. There was similar exposure-adjusted incidence of gastrointestinal events and fatigue and higher exposure-adjusted incidence of musculoskeletal and renal events with SoC compared with 177Lu-PSMA-617 + SoC suggesting an association with treatment exposure rather than 177Lu-PSMA-617. Dry mouth, dry eye and acute myelosuppression maintained a higher incidence, confirming relationship with 177Lu-PSMA-617 treatment. Conclusions: The adjusted safety analysis, accounting for a longer safety observation due to longer rPFS in patients receiving 177Lu-PSMA-617, reveals a comparable incidence of TEAEs between arms. This confirms a favorable risk/benefit profile of 177Lu-PSMA-617 added to SoC in this patient population. Clinical trial information: NCT03511664. [Table: see text]
Long-term safety of darolutamide in patients with metastatic castration-resistant prostate cancer.
Authors: Vjaters Egils , Fizazi Karim , James Nicholas D. , Tammela Teuvo , Matsubara Nobuaki , Priou Frank , Lesimple Thierry , Bono Petri , Kataja Vesa V , Garcia Jorge A. , Protheroe Andrew , Aspegren John , Joensuu Heikki , Kuss Iris , Thiele Silke , Fiala-Buskies Sabine , Jones Robert Hugh 
Published: February 2022

90 Background: Darolutamide, a structurally distinct and highly potent androgen receptor inhibitor, had a consistently favorable safety and tolerability profile in patients with nonmetastatic castration-resistant prostate cancer in ARAMIS, and discontinuation rates due to adverse events (AEs) remained consistently low after longer follow-up. In previously reported phase 1/2 studies in patients with metastatic castration-resistant prostate cancer (mCRPC), darolutamide was well tolerated for up to 25 months. We report the safety and tolerability of extended treatment with darolutamide in these mCRPC studies. Methods: Data from three phase 1/2 studies (NCT02363855, NCT01317641/NCT01429064, and NCT01784757) in patients with mCRPC were pooled for analysis of long-term safety. Results are summarized descriptively. Results: Of 173 patients with mCRPC evaluable for safety in the 3 studies, 13 patients received > 2 years of darolutamide treatment; median duration of treatment was 38 months (range 24–90). Six patients received > 4 years of darolutamide treatment. Nine of 13 patients with > 2 years of darolutamide therapy initially received 600 mg BID; others received 200 mg (n = 1), 300 mg (n = 1), or 700 mg (n = 2) BID. Median age was 68 years in the > 2-years group, and most patients were white. Patients were enrolled from France (n = 4), Latvia (n = 3), United Kingdom (n = 3), Finland (n = 2), and Japan (n = 1). Most patients had normal renal function (n = 10) and hepatic function (n = 10), 12 patients had Eastern Cooperative Oncology Group performance status of 0, and 9 patients had a Gleason score ≥7. Prior systemic anticancer treatments taken by more than 1 patient were bicalutamide (n = 10); cyproterone (n = 3); and triptorelin and leuprorelin (n = 2 each). No patient received prior chemotherapy. All 13 patients reported AEs, most grade 1 or 2; 6 reported grade 3 AEs. Treatment-related AEs were reported in 5 patients, and all were grade 1 in severity. Serious AEs were reported in 6 patients, and all were judged not related to darolutamide. One patient treated with darolutamide for > 2 years had an AE (new neoplasm; not related to darolutamide) that led to treatment discontinuation. Conclusions: Extended darolutamide treatment > 2 years in this small group of patients with mCRPC was generally well tolerated, with safety and tolerability consistent with that previously reported. Clinical trial information: NCT02363855, NCT01317641/NCT01429064, and NCT01784757.
Clinical utility of next-generation sequencing for prostate cancer in the context of a changing treatment landscape.
Authors: Griffin Jacqueline R. , Jun Tomi , Liaw Bobby Chi-Hung , Guin Sunny , Tsao Che-Kai , Patel Vaibhav G. , Rossi Michael , Zhou Xiang , Hantash Feras , Chen Rong , Oh William K. 
Published: February 2022

112 Background: Next-generation sequencing (NGS) is increasingly common in clinical practice, but its clinical utility may depend on the availability of sequencing-directed therapies (SDT). There were no FDA-approved SDTs in prostate cancer (PCa) until 2020, when PARP inhibitors olaparib and rucaparib were approved for tumors bearing alterations in certain homologous recombination repair (HRR) genes. We assessed the clinical utility of NGS in PCa before and after the approval of these agents in a single academic medical center. Methods: This was a retrospective single-center study including all PCa patients seen at Mount Sinai Hospital (New York, NY) between 2018–2021 who received NGS via the 161-gene Sema4 Signal Solid Tumor Panel. Clinical data were extracted from the Mount Sinai electronic medical record using a proprietary automated pipeline with limited manual curation (Sema4 PRODB). The primary outcome was clinical utility in metastatic PCa, defined as the proportion of metastatic PCa patients who received SDT. Secondary outcomes included time-to-next-treatment (TTNT, defined as time from SDT start to the start of next systemic therapy) and the proportion of patients with clinically actionable (as of 9/2021) alterations, defined as either Tier 1 (associated with FDA-approved treatments in prostate cancer) or Tier 2 (associated with either off-label or investigational agents). Results: The cohort consisted of 332 PCa patients; 51% (N = 170) were sequenced in 2020 or later. The median age at diagnosis was 65 (IQR 12). The most advanced stage documented was localized for 39% (N = 129) and metastatic for 61% (N = 203). Overall, 167 actionable alterations were identified in 125 patients (38% of cohort). Of the actionable alterations, 31% (N = 51) were Tier 1 and 69% (N = 116) were Tier 2. Of the 44 patients with Tier 1 alterations, 8 (18%) received SDT (all received olaparib). The proportion of metastatic patients receiving olaparib increased from 1% (2/145) before 2020 to 10% (6/58) during or after 2020 (p = 0.008). Of the 36 patients not receiving olaparib: 20 were sequenced before FDA approval and were treated with an alternative systemic therapy; 8 had localized disease and were not eligible; 8 had limited follow-up or unknown treatment status. For those who received olaparib, median TTNT was 5 months. Conclusions: In this single-center retrospective cohort, clinical utility of NGS was linked to treatment landscape. Increases in NGS test volume and olaparib use coincided with the approval of PARP inhibitors for patients with HRR-mutated prostate cancers. Notably, NGS was used to match patients to off-label/ investigational olaparib before its FDA approval.[Table: see text]
Updated biomarker results from a phase 1/2 study of olaparib and radium-223 in men with metastatic castration-resistant prostate cancer (mCRPC) with bone metastases (COMRADE).
Authors: McKay Rana R. , Xie Wanling , Ajmera Archana , Saraiya Biren , Parikh Mamta , Folefac Edmund , Olson Adam C. , Heath Elisabeth I. , Parikh Rahul Atul , Ivy S. Percy , Van Allen Eliezer Mendel , Lindeman Neal Ian , Shapiro Geoffrey 
Published: February 2022

119 Background: Radium-223 is an α-emitting radioisotope that induces DNA double-strand breaks leading to cell death. In preclinical models, PARP inhibitors have shown efficacy as radiosensitizing agents. We designed a phase 1/2 trial to test the safety and efficacy of radium-223 + olaparib. Tissue based studies investigated homologous recombination repair (HRR) gene status. Methods: This was an open-label, multi-center, phase 1/2 study (NCT03317392) evaluating the dosing, safety and efficacy of radium-223 + olaparib. Eligible patients (pts) had mCRPC with ≥2 bone metastases without visceral metastases or lymphadenopathy > 4 cm. There was no limit on prior therapy. All pts had a baseline biopsy and archival tissue was collected when available. The phase 1 used a 3+3 dose escalation design with fixed dose radium-223 (55 kBq/kg IV every 4 weeks x 6). Dose level 1 (DL1) was olaparib 200 mg PO BID; DL2 was olaparib 300 mg PO BID. The primary objective was to determine the recommended phase 2 dose (RP2D). Secondary objectives included radiographic progression-free survival (rPFS) (PCWG3 criteria), PSA response (50% decline from baseline), and alkaline phosphatase response (30% decline from baseline). HRR gene status was determined using Oncopanel tissue profiling. Results: 12 pts were enrolled on the phase 1. Median age was 68 (range 59-81) years. Median prior lines of CRPC therapies was 2 (1-5), including 3 (25%) who had received prior chemotherapy and 12 (100%) a prior novel hormone therapy. The RP2D of olaparib was 200 mg BID when combined with radium-223. Overall, PSA response and alkaline phosphatase response were 16.7% (n=2) and 67% (n=8), respectively. Median follow-up was 6.5 (range 2.8, 11.8) months, and 6-month rPFS was 57% (95% CI: 25%, 80%). 9 patients had available tissue for Oncopanel testing (7 from baseline metastasis biopsy; 2 from archival prostate tissue). Two patients were identified to have pathogenic HRR gene alterations: 1 patient with a BRCA2 mutation with rPFS of 11.63 months, 1 patient with CDK12 mutation with rPFS 2.60 months (Table). Conclusions: We demonstrate that olaparib can be safety combined with radium-223 with RP2D of 200 mg BID. Though limited by sample size, we demonstrate prolonged disease control in a pt with a BRCA2 mutation receiving radium-223 + olaparib. Additional profiling from the currently accruing phase 2 study of radium-223 +/- olaparib will further elucidate biomarkers of response. Clinical trial information: NCT03317392. [Table: see text]
Triplet therapy in metastatic castration-sensitive prostate cancer: A systematic review and meta-analysis.
Authors: Naqvi Syed Arsalan Ahmed , Riaz Zaryab Bin , Riaz Anum , Islam Mahnoor , Siddiqi Rabbia , Ikram Waleed , Jafar Muhammad Ali , Singh Parminder , Ravi Praful Kumar , Riaz Irbaz Bin , Bryce Alan Haruo 
Published: February 2022

136 Background: Intensification of initial treatment of in patients with metastatic castration-sensitive prostate cancer (mCSPC) with androgen pathway inhibition (API) in addition to docetaxel (DOC) and androgen deprivation therapy (ADT) has shown promise to improve clinical outcomes. Thus, we synthesize the data from modern clinical trials to estimate overall estimates of progression and survival outcomes. Methods: A systematic search of electronic databases (MEDLINE and EMBASE) was conducted to include phase III randomized controlled trials (RCTs) evaluating triplet therapy (API+DOC+ADT) against doublet therapy (DOC+ADT) in mCSPC. Outcomes of interest included overall survival (OS) and radiographic progression-free survival (rPFS). A DerSimonian-Laird random-effects meta-analysis was performed to pool precomputed hazard ratios (HRs) and confidence intervals (CIs) after logarithmic transformation using inverse-variance weighting approach. Cochran’s Q statistical test was used to assess statistically significant heterogeneity not explained by chance, while I2 statistical test was used to quantify the total observed variability, due to between-study heterogeneity. I2 values >50% indicated substantial heterogeneity. A summary of findings table was constructed to translate relative estimates to absolute risks. Results: A total of 1,531 patients in four RCTs with direct comparative data between triplet and doublet therapies, were included in this meta-analysis. PEACE-1 was the only RCT directly assessing this question (AAP+DOC+ADT). ENZA+DOC+ADT was evaluated as a subgroup in two RCTs (ENZAMET; ARCHES), APA+DOC+ADT was evaluated as a subgroup in one (TITAN). To be able to pool studies, the relative efficacy of control arm in ENZAMET (first generation bicalutamide + ADT) was considered equivalent to ADT based on prior literature. A total of 672 rPFS events were observed (34%; 261 events in triplet therapy, 54%; 411 events in doublet therapy). The difference was statistically significant (HR: 0.49; 95% CI: 0.42-0.58; I2: 0%). Similarly, 469 OS events were observed (28%; 217 events in triplet therapy, 33%; 252 events in doublet therapy). The difference was statistically significant (HR: 0.80; 95% CI: 0.67-0.96; I2: 0%). The summary of findings is outlined in the table. Conclusions: The results of this meta-analysis support an improvement in rPFS and OS in favor of triplet therapy over doublet therapy for mCRPC. However, comparative effectiveness of different triplet regimens may be different and needs further exploration.[Table: see text]
PRIMERA trial (NCT04188275), early survival results from a prospective trial exploring impact of circulating tumor cell detection in castrate resistant prostate cancer patients undergoing abiraterone or enzalutamide I line treatment.
Authors: Francolini Giulio , Loi Mauro , Ciccone Lucia Pia , Mangoni Monica , Detti Beatrice , Di Cataldo Vanessa , Aquilano Michele , Allegra Andrea , Pinzani Pamela , Salvianti Francesca , Cerbai Cecilia , Burchini Luca , Frosini Giulio , Mattioli Chiara , Salvestrini Viola , Guerrieri Barbara , Salvatore Giulia , Sottili Mariangela , Desideri Isacco , Livi Lorenzo 
Published: February 2022

137 Background: Circulating tumor cells (CTC) detection and androgen receptor splice variant 7 (ARV7) expression have been shown to be associated with worse clinical outcomes in metastatic castration resistant prostate cancer (mCRPC) patients undergoing androgen receptor targeted agents (ARTA) treatment, paving the way for alternative treatment options for patients with negative predictive factors. Full-length androgen receptor (ARFL), prostate specific membrane antigen and prostate specific antigen (PSA) may further help to refine prognostic models. In our institution, a prospective observational trial testing CTC detection in mCRPC undergoing ARTA treatment (PRIMERA trial, NCT04188275) terminated the planned enrollment in 2020. Here we present early results of the overall cohort. Methods: PRIMERA (NCT04188275) is a prospective, observational trial enrolling mCRPC patients undergoing ARTA treatment. All patients were treated with either abiraterone or enzalutamide in I line setting. Blood samples to detect CTCs were taken before starting ARTA treatment. Reverse transcription - quantitative real-time PCR (RT-qPCR) was used to determine the CTC expression of PSA, PSMA, AR and ARV7. PSA drop (defined as difference between baseline PSA at ARTA treatment start and PSA at nadir under treatment), progression free and overall survival (PFS and OS) and their correlation with CTC detection were reported. Explorative analysis about AR, PSA and PSMA expression in CTC+ patients were conducted. Results: Overall, 44 patients were included. CTC were detected at treatment start in 19 patients (43,2%), of whom 3(15,78%), 9(63,15%), 15(78,94%) and 14 (73.68%) patients expressed ARV7, ARFL, PSA and PSMA, respectively. Biochemical response was significantly improved in CTC+ vs. CTC- patients, with median PSA drop values of 18.5 vs 2.5 ng/ml (p=0.03). After a median follow up of 18 months, 22 (50%) patients progressed. PFS was significantly longer in CTC- patients (not reached vs 16 months, respectively, p=0.02). Eight (18.2%) patients died, a non-significant trend in terms of overall survival was detected in favor of CTC- patients (not reached vs 29 months, respectively, p=0.05). AR, PSA and PSMA expression in CTC+ had no significant impact on PSA drop, PFS or OS. Conclusions: PRIMERA trial confirmed the CTC detection predictive importance in mCRPC patients. Adequately powered studies will be needed to further explore CTC profiling in this setting. Clinical trial information: NCT04188275.