bluuebunny/crossref_metadata_2025_split huggingface dataset:
Remote delivery of cancer genetic testing in veterans with metastatic prostate cancer: A Million Veteran Program study.
Authors: Montgomery Robert Bruce , Lynch Julie Ann , Brown Jessica , Maxwell Kara Noelle , Kabilovic Nismeta , Stoll Katie , Simon Julie , Kogan Maria , Whitbourne Stacey , Gaziano J. Michael , Cheng Heather H. , Etzioni Ruth Douglas , Pritchard Colin C. 
Published: January 2024

60 Background: Germline pathogenic alterations are found in approximately 10% of men with metastatic prostate cancer (mPC) and can inform precision therapy, surveillance, and cancer prevention for family. National guidelines recommend germline genetic testing be offered to all men with mPC, yet uptake of testing in the community has been documented to be 6-12% with many barriers to testing. We conducted a study to determine uptake of testing using remote consenting and testing for veterans with mPC who had participated in the Veteran’s Administration Million Veteran Program (MVP). We wanted to know if remote testing could overcome limited point-of-care counseling and ordering to increase uptake of germline testing. Methods: This prospective study enrolled veterans who participated in MVP study with a diagnosis of mPC. Veterans were contacted by mail with an option to opt-out of further contact. Those who did not opt-out were mailed information regarding the study and received a follow-up phone call to establish interest in germline testing with a CLIA-level germline test (BROCA). Those expressing interest provided verbal informed consent and were mailed a saliva collection kit for a multigene cancer predisposition gene panel test (University of Washington). Results were disclosed by phone and mailed to the patient with genetic counseling support and was also sent to the oncology provider by email, phone or both. Two research coordinators and two part-time genetic counselors provided review of consenting, counseling and return of results. Results: As of September 17, 2023, 1952 veterans who were alive with an incident diagnosis of mPC were identified through MVP and did not opt out of further contact. Informational letters were sent to the home address of all eligible participants. 681 (22%) of veterans were reached and completed informed consent. All participants were then sent a saliva kit and 432 (63%) completed testing, with 23 tests currently pending. Among the participants, 70% were White, 21% were Black, 0.5% Asian and 8% unknown. Thirteen percent (53/409) were found to have a germline pathogenic variant. Conclusions: We evaluated uptake of germline testing using a remote, VA system-wide approach to identify and offer genetic testing for veterans with mPC with access and cost issues removed. We completed germline testing at rates significantly higher than those reported in the community with modest personnel requirements, while also reaching a more diverse population of patients. Remote genetic testing can improve uptake of testing in large integrated health care systems.
Avelumab first-line (1L) maintenance for advanced urothelial carcinoma (aUC): Long-term outcomes from the JAVELIN Bladder 100 trial in patients (pts) with high body mass index (BMI).
Authors: Aragon-Ching Jeanny B. , Petrylak Daniel P. , Sridhar Srikala S. , Gupta Shilpa , Grivas Petros , Powles Thomas , Gurney Howard , Jacob Natalia , Tyroller Karin , Guenther Silke , Bellmunt Joaquim 
Published: January 2024

600 Background: Avelumab 1L maintenance is recommended as standard of care by international treatment guidelines for pts with aUC that has not progressed with 1L platinum-based chemotherapy, based on level 1 evidence from the phase 3 JAVELIN Bladder 100 trial (NCT02603432). In the trial, avelumab 1L maintenance + best supportive care (BSC) significantly prolonged overall survival (OS) and progression-free survival (PFS) vs BSC alone (median OS, 23.8 vs 15.0 mo; HR, 0.76 [95% CI, 0.63-0.91]; 2-sided p=0.0036). The long-term safety of avelumab 1L maintenance was also demonstrated. It is estimated that 25% of the world’s population will have BMI ≥30 by 2035, and high BMI is a risk factor for bladder cancer. We report post hoc analyses of long-term outcomes from JAVELIN Bladder 100 in pts with high BMI (≥30) at baseline. Methods: Eligible pts with unresectable locally advanced or metastatic UC without progression after 4-6 cycles of 1L platinum-based chemotherapy were randomized 1:1 to receive avelumab 10 mg/kg every 2 wk + BSC (n=350) or BSC alone (n=350). The primary endpoint was OS; secondary endpoints included PFS and safety. Results: At data cutoff (June 4, 2021), median follow-up was ≥38 mo in both arms. In the avelumab + BSC and BSC alone arms, 67 and 55 pts had high BMI at baseline, respectively. In these pts, median OS was 20.8 mo (95% CI, 16.9-34.4) with avelumab + BSC vs 12.7 mo (95% CI, 8.1-26.6) with BSC alone (HR, 0.77 [95% CI, 0.49-1.21]); 2-y OS rates were 47.8% vs 37.6%, respectively. Median PFS by investigator was 5.6 mo (95% CI, 3.7-7.5) with avelumab + BSC vs 2.1 mo (95% CI, 1.9-4.0) with BSC alone (HR, 0.64 [95% CI, 0.42-0.97]); 2-y PFS rates were 23.5% vs 11.3%, respectively. Long-term safety in pts with high BMI was generally consistent with the overall safety population (Table). Conclusions: This exploratory analysis shows the long-term efficacy and tolerability of avelumab 1L maintenance in pts with high BMI in JAVELIN Bladder 100, with no new safety concerns identified. These results further support the use of avelumab 1L maintenance as standard of care in pts with aUC who are progression free after 1L platinum-based chemotherapy, including pts with high BMI. Clinical trial information: NCT02603432 . [Table: see text]
A retrospective cohort study to monitor real-world safety in patients with locally advanced or metastatic urothelial carcinoma (LA/mUC) treated with sacituzumab govitecan (SG) in the United States.
Authors: Parikh Mamta , Boateng Freda , Eng Susan , Sierecki Mitch , Chen Fangfei , Brockman Jane Michelle , Ghazi Youssef , Ng Leslie 
Published: January 2024

608 Background: Patients with LA/mUC experience poor outcomes, with few treatment options historically available. In April 2021, SG (a TROP-2-directed antibody drug conjugate) received accelerated approval for patients with LA/mUC who progressed after platinum-based chemotherapy and immune checkpoint inhibitor therapy, based on the pivotal TROPHY U-01 trial (NCT03547973). We sought to evaluate SG safety in patients with LA/mUC treated in routine clinical practice in this study. Methods: A retrospective cohort of patients aged ≥ 18 years with LA/mUC treated with SG in the United States was evaluated using data from the nationwide Flatiron Health electronic health record–derived de-identified database (from Jan 2011 to Oct 2022). Outcomes included patient characteristics, treatment patterns, adverse events (AEs) of interest incidence, and granulocyte-colony stimulating factor (G-CSF) use. Descriptive statistics were used for data analysis. Results: This study included 86SG-treated patients (male, 70%; median age, 71 [range: 25-85] years; 27% with ECOG ≥ 2; 84% treated in community settings). Most patients (71%) received enfortumab vedotin (EV) in the direct prior line. The majority of patients received SG as monotherapy (94%), with most patients overall (99%) receiving SG as second-line (2L) or later. The most common AEs of interest (any grade, overall) were diarrhea (35%), neutropenia (40%) and nausea/vomiting (21%) (Table). Of the 86 patients, 14 (16%) patients were hospitalized, 8 (9%) discontinued SG treatment likely due to AEs/toxicity, and 3 (3%) died during or within 7 days after the line of treatment. During SG treatment, 52% of patients used G-CSF (primary prophylaxis 24%; secondary prophylaxis 19%; therapeutic use 28%). Only 1 (4.5%) patient who had primary G-CSF prophylaxis developed grade ≥ 3 neutropenia. Conclusions: This study is the largest analysis of SG use in a real-world population with LA/mUC to date; it provides insights into the safety of SG in this setting. Compared with prior data, this real-world population was older, with poorer functionality, and the majority received EV in the direct prior line. Observed AEs were consistent with the known safety profile of SG and indicate that this sequencing is feasible. [Table: see text]
Punch: Preliminary results from a phase II study of intra-arterial chemotherapy (IAC) combined with tislelizumab and bacillus Calmette-Guerin (BCG) in high-risk non-muscle-invasive bladder cancer (HR NMIBC).
Authors: Wang Zongren , Zhan Wenhao , Huang Bin , Luo Cheng , Chen Lingwu , Chen Junxing 
Published: January 2024

618 Background: Previous studies have proved IAC could reduce the recurrence and progression of HR NMIBC. The KEYNOTE-057 study has supported the benefits of PD-1 inhibitor in HR NMIBC patients (pts). Our study was established to evaluate the efficacy and safety of IAC combined with tislelizumab and BCG as a bladder-preserving treatment for HR NMIBC pts. Methods: This open-label, single arm phase II study enrolled BCG-naïve HR NMIBC pts with papillary tumors (high-grade Ta or T1 tumors). Firstly, the papillary tumors should be removed all visible lesions by transurethral resection of bladder tumor (TURBT). Secondly, angiographic catheter was placed into the internal iliac arteries with Seldinger’s percutaneous technique, cisplatin (60 mg/m2) and epirubicin (50 mg/m2) were administered arterially in day 1 (D1), every 3 weeks for 2-4 cycles. And pts received tislelizumab 200 mg IVGTT in D1, every 3 weeks for 2-4 cycles. Finally, pts received 18 instillations of BCG plus at least 8 cycles of tislelizumab (200 mg IVGTT, every 3 weeks). Specifically, pts were started on an induction course of BCG with 6 instillations every week, followed by maintenance with 3 instillations every 2 weeks and 9 instillations every 4 weeks. The primary end point was disease-free survival (DFS) rate at 12 months (defined as no reappearance of high grade or T1 tumors or clinical stage development after the therapy). Secondary end points were bladder-preservation rate, OS and safety. Our study estimated a DFS rate at 12 months was no less than 55% and the study would enroll 27 pts. Results: By Sep. 2023, 13 eligible pts were enrolled. Ten pts were analyzed (male 80.0%; median age 58 years (39-77); pure TCC 80.0%; median tumor size 2.5 cm (0.6-5.4); multiple papillary tumours=60.0%; high-grade Ta=40.0%, T1=60.0%). Median follow-up was 16.4 months (10.8-33.9), the mean number of IAC cycles was 2.4, mean number of tislelizumab cycles was 15.8, and the median BCG instillations was 16 (11-18). The DFS rate at 12 month was 90.0% (95%CI, 71.5%-98.6%). One pt showed reappearance of high-grade Ta and received TURBT. The bladder-preservation rate at 12 months was 100% (95%CI, 100%-100%). The OS rate at 12 months was 100% (95%CI, 100%-100%). 3 pts experienced treatment related adverse events, including nausea (n=1, G2), myalgia (n=1, G2), fatigue (n=1, G2), neutropenia (n=1, G2) and fever (n=1, G3). Conclusions: Our preliminary results supported the use of IAC combined with tislelizumab and BCG as a promising bladder-preserving strategy for HR NMIBC pts. Clinical trial information: ChiCTR2200067146 .
PEMBROBLAD: Real world effectiveness and safety of immune checkpoint inhibitors in patients with advanced urothelial carcinoma with histological variants.
Authors: Amrane Karim , Campedel Luca , Bennamoun Mostefa , Gabriel Pierre-Etienne , Brouchet Nicolas , Pouessel Damien , Roulleaux Dugage Matthieu , Thibault Constance , Cancel Mathilde , Gout Mathilde , Flechon Aude , Huillard Olivier , Abbar Baptiste , Borchiellini Delphine , Doublet Louis , Augusto-Pelegrin Laetitia , Elouen Boughalem , Moinard-Butot Fabien , Dumont Clement , Barthelemy Philippe 
Published: January 2024

624 Background: A non-negligible portion of bladder cancers have non-pure UC histology; these tumors are often underdiagnosed and represent an unmet treatment need. Efficacy of immune checkpoint inhibitors (ICI) in non-pure UC remains unknown. We report preliminary data form the PEMBROBLAD study assessing ICI in pretreated mixed variants (UC-V) or pure non-UC (NUC) in real life condition. Methods: PEMBROBLAD is a retrospective multicenter study conducted in 24 French GETUG centers. Eligible patients had advanced UC with UC-V or NUC. All patients received ICI as a second line treatment. We excluded patients with ICI maintenance therapy. The primary endpoint was overall survival (OS); secondary endpoints included overall response rate (ORR), progression free survival (PFS), time to treatment failure (TTF) and safety. Results: A total of 139 patients (pts) were analyzed. Median age was 70 years (range 44-88), 70.8 % were male with ECOG PS 0/1, 2 and 3 in 57.7%, 26.6% and 10.1% of cases respectively. The most common variants of UC-V (n=96, 69.0%) were squamous cell differentiation (n=25, 26.0%), sarcomatoid (n=12, 12.5%), micropapillary (n=9, 9.3%), neuroendocrine (n=8, 8.3%), nested (n=7, 7.3%) and adenocarcinoma (n=5, 5.2%); squamous cell carcinoma (n=23, 53.4%) represented the majority of NUC (n=43, 31.0%). At data cutoff (August 15, 2023), median follow-up was 35.1 months (mo) (range 3.7-86.9). The most administered ICI was pembrolizumab in 85.6% of cases followed by durvalumab in 12.2% of cases. Median OS was 6.1 mo for all pts, 6.1 and 5.9 for UC-V and NUC respectively. In pts with UC-V and NUC, ORR was 31.2 % (n=30) and 18.6% (n=8) and DCR was 41.6% (n=40) and 23.2% (n=10) respectively. In all 139 pts, median TTF was 2.2 mo (95% CI, 0.1-50.0 mo). Serious TRAE occurred in 13 pts (9.3%). Discontinuation due to TRAEs occurred in 5.0% of pts. Conclusions: Our results suggest some efficacy of ICI in pretreated advanced UC-V and NUC. No new safety concerns were identified. Updated results with subgroup analysis will be reported at the meeting. [Table: see text]
Randomized phase III clinical trial of neoadjuvant intravesical mitomycin C (MMC) treatment in patients with primary treatment-naïve vesical neoplasms: Interim analysis.
Authors: Saita Alberto , Hurle Rodolfo , Arena Paola , Pozzi Chiara , Cieri Miriam , Colombo Piergiuseppe , Lazzeri Massimo , Lughezzani Giovanni , Buffi Nicolò Maria , Fasulo Vittorio , Paciotti Marco , Mancon Stefano , Lizier Michela , Morenghi Emanuela , Rescigno Maria , Casale Paolo 
Published: January 2024

626 Background: The aim of the current study is to evaluate the safety, tolerability, and efficacy of neoadjuvant MMC in patients (pts) with non-muscle invasive bladder cancer (NMIBC). Methods: This is a prospective phase III randomized clinical trial in pts with primary clinical diagnosis of urinary bladder cancer or secondary recurrent untreated bladder cancer since May 2022 to September 2023 (EudraCT 2021-003751-42_studio ICH-013-). Pts are randomized 1:1 to neoadjuvant MMC arm (neoA) or standard arm (StA). In the 2 weeks before scheduled TUR (day 0) neoA pts receive intravesical instillations of MMC (40 mg/40 ml saline) at day -14 and -7 and cystoscopy with a cold cup biopsy at -14. After TUR, clinical choices both in the two groups, depend on histological evaluation of the tumour and EAU guidelines. Midstream and catheter urines are collected before instillations, at day 0 and after 3 months to respectively measure the level of specific biomarker (i.e., HMGB1) and to identify the microbiota. The expression of a mitomarker is evaluated on tissue samples. The primary endpoint is to assess safety, tolerability, and efficacy of neoadjuvant MMC in reducing the recurrence rate of BC calculated as the proportion of pts who achieve a complete response (no evidence of BC after 3, 6, 12 and 24 mo). The secondary endpoint will be the analysis of the rate of grade and stage progression to MIBC in case of recurrence and the correlation with biomarkers. Results: The interim analysis (median follow-up 6 months) included 54 pts: 26 in the StA and 28 in the neoA. Respectively in StA and neoA mean age at TUR was 66.5 (±9.9) and 65.8 (±9.9), males were 23 (88.46%) and 24 (85.71%). No statistically significant difference was observed between groups. 5 neoA pts [17.86% (95%CI 6.06-36.89)] after instillations reported 4 different adverse reactions, grade 1 of Clavien Dindo classification. NeoA pts showed higher level of HMGB1 at day 0 and after 3 months, suggesting an increased induction of immunogenic cell death (ICD). Shotgun metagenomics on microbial DNA from catheter urine is still ongoing. In field recurrence has been observed in 1 (3.85%) StA and 2 (7.14%) neoA pts. Conclusions: Preliminary data show neoadjuvant MMC to be safe and well tolerated and seem to correlate with increase of HMGB1. The short follow-up and the small sample size do not allow conclusion on the efficacy. Clinical trial information: EUCTR2021-003751-42 .
Clinical and patient factors associated with treatment intensification for metastatic castration-sensitive prostate cancer.
Authors: Appukkuttan Sreevalsa , Williams Troy , Jhaveri Jay , Campbell David , Kong Sheldon , Kalayeh Bashir , Ramsey Scott David 
Published: January 2024

63 Background: Intensified therapies convey a survival advantage over androgen deprivation therapy (ADT) alone in metastatic hormone sensitive prostate cancer (mHSPC). We sought to identify area- and patient-level factors that are associated with intensification of therapy among mHSPC patients treated in US health systems. Methods: Electronic health records from OPTUM were used to identify patients aged ≥18 with mHSPC who received ADT between 2020 and 2022. Treatment intensification was defined as receiving one of the following within 90 days of initiation of ADT: apalutamide, enzalutamide, abiraterone +/- prednisone +/- docetaxel, darolutamide +/- docetaxel, docetaxel +/- other systemic therapy, and external beam radiation therapy (EBRT). Multivariable logistic regression was used to determine factors associated with intensification. We used Chi-squared tests to select the model with the best statistical fit. Results: We identified 1,123 patients with mHSPC who received ≥1 ADT in the post-index period with mean age of 71.2 (9.5), 73% Caucasian, 18% African American, and 2% Asian. Overall, 640 (57%) patients received treatment intensification within 90 days of ADT initiation. The proportion of patients receiving intensification increased from 53% to 63% between 2020 and 2022. The most common intensification treatments were abiraterone acetate (46%) and enzalutamide (38%). The median time to first treatment after metastasis was 15 days for receiving intensified therapy and 34 days for non-intensified therapy. In multivariable logistic regression, younger age, presence of bone/bone marrow metastasis at baseline, region (Northeast and West), and lower modified Charlson Comorbidity Index (CCI) score (excluding cancer) were significantly associated with receiving intensified therapy (Table). PSA was not included in models due to substantial missingness (40%). Conclusions: Just over half of eligible patients received treatment intensification following ADT. There are also significant disparities in treatment by age, region, and site of metastases. Future studies examining physician and patient preferences for intensification, as well as possible misperceptions and biases, would provide evidence to address undertreatment in this setting. [Table: see text]
GCISAVE: A non-comparative randomized phase II study of combination of gemcitabine cisplatin (GCis) +/- avelumab (A) in 1st line treatment for locally advanced or metastatic urothelial bladder carcinoma (MUBC)—GETUG AFU V07.
Authors: Gross-Goupil Marine , Frison Eric , Roubaud Guilhem , Flechon Aude , Calcagno Fabien , Rolland Frederic , Joly Florence , Raymond Anne-Aurelie , Chotard Guillaume , Barthelemy Philippe , Pouessel Damien , Thibault Constance , Culine Stephane , Linassier Claude , Ravaud Alain 
Published: January 2024

637 Background: GCis is the standard 1st line of MUBC. Immune Checkpoint Inhibitor (ICI) is indicated as maintenance with avelumab (A), in patients (pts) with objective response or stable disease after chemotherapy, or as 2ndline with Pembrolizumab, in case of disease progression. Survival improvement of combining ICI to GCis still remains under investigation. GCISAVE evaluates the efficacy and safety of combining avelumab (A) with GCis in 1st line treatment. Methods: GCISAVE is a prospective multicenter randomized (2:1) non-comparative open-label phase II study, assessing the efficacy and safety of 6 cycles of GCis +/- A on a two-stage Bryant-Day design. Pts fit for cisplatin received GCis (G 1000 mg/m2, D1,D8; Cis 70 mg/m2, D1) +/- A (10 mg/kg, D1), every 3 weeks. Stratification was on centre, Karnofsky and visceral vs. non-visceral metastases. Two co-primary endpoints were the objective response rate (ORR) at week 18 (target≥ 60%) and the incidence of grade ≥3 treatment related adverse events (TRAE) (target<30%). Secondary objectives included: duration of response, 18 month PFS and OS;describing ORR according to the expression of PD-L1, immune infiltrate population and proteomics. Results: Between 11/2017 and 11/2020, 65 pts have been included, 42 (GCis+A) and 23 (GCis). Study was stopped prematurely due to the approval of A as maintenance treatment. Clinical characteristics were well balanced. 20 pts (47.6 %) in GCis + A arm and 7 pts (31.8 %) in GCis arm achieved 6 cycles with cisplatin : male (83.3 and 81.8%), median age (68 (62-71) and 67(56-72) yo), M1 stage for 76.2 and 77.3% respectively. 18 pts (42.9 %) in GCis + A and 13 pts (59.1 %) in GCis crossed to carboplatin. At week 18, ORR was 79.5% in the (GCis+A), including 15% Complete Response (RC) (39 pts evaluable), and 59.1% (GCis) arm (22 pts evaluable) respectively. TRAE were reported in 11 pts (26.2 %) in GCis+A arm. An oncoprot signature was obtained for CR and Partial Response compared to Progressive Disease (PD). Conclusions: GCis+A achieved the predefined target values with ORR ≥60% and ≤30% of SAE in 1st line treatment of MUBC. An oncoprot panel seemed to be correlated to PR, CR vs. PD. Clinical trial information: NCT03324282 .