bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oncologic outcomes of neoadjuvant chemotherapy and lymph node dissection with partial cystectomy for muscle-invasive bladder cancer.
Authors: Antar Ryan Michael , Xu Vincent Eric , Gordon Olivia French , Farag Christian Mark , Azari Sarah , Whalen Michael Joseph 
Published: January 2024

698 Background: Partial cystectomy (PC) offers potential benefits for select patients with muscle-invasive bladder cancer (MIBC). However, the oncologic efficacy of PC may be compromised due to the underutilization of standard-of-care modalities, such as neoadjuvant chemotherapy (NAC) and pelvic lymphadenectomy (PLND). We aimed to assess factors influencing the incorporation of NAC and PLND with PC and evaluate their impact on overall survival (OS). Methods: We identified patients with cT2-4N0M0 BCa who underwent PC between 2004 and 2019 using the National Cancer Database (NCDB). The primary endpoint was OS. Kaplan-Meier analysis compared OS between PC patients who did and did not receive NAC. Multivariate Cox Proportional Hazards (CPH) model assessed the impact of age, sex, race, insurance, income, Charlson-Deyo Index (CDI), clinical T-stage, facility type, histology, surgical margins, NAC, PLND adequacy (≥10 LN yield), and adjuvant radiation treatment on OS. Multivariate logistic regressions were performed to examine predictors of NAC and PLND receipt in PC patients. Results: Of 2,832 patients included, 231 (8.1%) patients received multi-agent NAC with PC and had improved median OS compared to those who did not (115.0 vs. 87.4 months, p<0.001). This finding persisted in the adjusted CPH model, where private insurance, NAC, and PLND significantly improved OS, especially when PLND yielded ≥10LN. Conversely, age >80, CDI >2, cT3-4, positive margins, and adjuvant radiation all increased adjusted mortality risk. After controlling for clinicopathologic variables, females were less likely to receive PLND (OR=0.634, p<0.001), while NAC was more likely administered to PC patients diagnosed from 2015-2019 (OR=2.177, p=0.022). PC patients who received NAC were more likely to have PLND performed as part of their treatment regimen (OR=2.189, p<0.001). Additionally, patients treated at academic centers were more likely to have NAC administered and PLND performed (OR=1.745, p=0.003; OR=2.465, p<0.001, respectively). Conclusions: Despite guidelines, there is an insufficient utilization of NAC and PLND when performing PC. Our analysis underscores the significant OS benefit of these recommended treatments as part of MIBC care. Importantly, we highlight a gradual increase in NAC and PLND receipt in recent years, centered largely at academic facilities. Notably, gender disparities exist in PLND receipt, emphasizing the need for further investigation. [Table: see text]
Survival and comorbid diabetes mellitus in metastatic hormone-sensitive prostate cancer.
Authors: Baxi Priya , Eaton Daniel B. , Puri Varun , Schoen Martin W. 
Published: January 2024

74 Background: Diabetes is increasing in prevalence and management of comorbid disease in cancer is important for outcomes. Comorbid diabetes mellitus in patients with metastatic hormone sensitive prostate cancer (mHSPC) is important to consider as cancer treatments can adversely affect metabolic health and have added interactions with diabetes medicines. Little is known about the comparative effectiveness of diabetes management with insulin or oral medications. We aim to assess the survival of patients with comorbid diabetes based on insulin, oral, or no medication management. Methods: Patients diagnosed with mHSPC from 2000-2021 were identified within the Veterans Health Administration. Uncomplicated or complicated diabetes was determined using Charlson codes from the International Classification of Diseases. Treatment was determined by prescriptions of insulin, oral medication, or no use in VHA prescription records in the year prior, up to 14 days before diagnosis. Kaplan-Meier, ANOVA, and Cox proportional hazard models were used to analyze the data and covariates such as body-mass index, age, race, and baseline PSA. Results: Patients with mHSPC had significant differences in survival with diagnosis of diabetes, see table. Patients with complicated diabetes had a higher mean BMI than patients with uncomplicated diabetes (28.3 vs. 29.1, p <.001). In patients with diabetes (n = 4740), insulin was used in 1091, oral medication in 1833, or no medicines in 1816. Oral diabetes medication was associated with improved survival compared to insulin and no medication use had the lowest survival (26.6 months vs. 24.3 vs. 21.9, p <0.001). In an adjusted multivariable model, both insulin and oral medicine use were associated with increased risk of death with adjusted Hazard Ratio (aHR) for insulin 1.25 (95% CI 1.17-1.35), for oral medicine aHR 1.11 (95% CI 1.05-1.18). Conclusions: Among veterans with mHSPC, diabetes was associated with decreased survival. Within patients with a diagnosis of complicated or uncomplicated diabetes, the use of oral medication was associated with longer survival compared to insulin. Further assessment of the management of comorbid diabetes may help guide treatment and prevent adverse events. [Table: see text]
Implementation outcomes of a multidisciplinary approach for Lu177-PSMA-617 therapy.
Authors: Nedrud Marybeth , Wang John , Maldonado Grijalva Valeria , Kelleher Colm , Wong Terence Z. , McManus Hannah Dzimitrowicz , Labriola Matthew 
Published: January 2024

80 Background: Lu177-PSMA-617 (LuPSMA) is a recently approved treatment for patients with metastatic castration resistant prostate cancer (mCRPC). Successful treatment in real-world practice requires coordination between nuclear medicine, radiation safety, and medical oncology. We report outcomes from implementation of a multidisciplinary approach for LuPSMA administration at our institution. Methods: Our practice prior to treatment included collaborative radiologist review of PSMA PET/CT and oncologist review of prior therapies, performance status, and baseline laboratory values to establish candidacy. For each administration, procedures included confirming IV patency, use of a shielded infusion pump, IV hydration, and standardized radiation safety recommendations. On treatment, practices included scheduled laboratory monitoring, standardized treatment holds and dose reductions, coordination of care with a dedicated advanced practitioner, and mid-treatment conventional imaging. Retrospective chart review was completed for 100 mCRPC patients who received ≥1 dose of LuPSMA from June 2022 to August 2023 under this protocol. Outcomes including number of treatments, dose reductions/holds, PSA, and clinical imaging responses were reviewed. Results: Ninety-eight patients were included in the analysis (2 patients were excluded due to prior LuPSMA on clinical trial). In patients completing LuPSMA at time of data collection, median number of treatments was 4.0 (IQR=4.0, n=95), with 41% receiving all 6 planned treatments (n=39/95). During treatment, 16% experienced a treatment hold (n=16/98) with 25% ultimately completing 6 treatments (n=4/16; median=3.0, IQR=3.25). Holds were due to worsening symptoms (44%, n=7/16) or cytotoxicity (44%, n=7/16). Dose reductions occurred in 8% (n=8/98), with 38% completing 6 treatments (n=3/8; median treatments= 4.5, IQR= 3.0). Early discontinuation primarily occurred due to clinician-assessed progression (57%, n=32/56) or cytotoxicity (25%, n=14/56). Of those with early discontinuation due to progression, 70% had a rising PSA at time of discontinuation (n=21/30) and all had worsening disease on available mid-treatment imaging (n=15/15). For the remainder with early discontinuation due to progression, 20% had stable PSA (n=6/30) and 10% had decreasing PSA at time of discontinuation (10%, n=3/60). In those with stable or rising PSA, 75% terminated treatment due to worsening disease on available mid-treatment imaging (n=6/8). Conclusions: Our protocol for LuPSMA administration allows for early identification of clinical progression and completion of therapy when appropriate. Treatment holds and dose reductions facilitate therapy completion in select patients. Mid-treatment imaging may identify worsening disease in the setting of stable or decreasing PSA, underlying the potential importance of this practice for clinical decision making.
Patient characteristics, treatment patterns, and outcomes among early adopters of lutetium Lu 177 vipivotide tetraxetan (177Lu-PSMA-617): A real-world United States (US) study.
Authors: Wei Xiao X. , George Daniel J. , Patel Jeetvan , Nguyen Jennifer , Kang Barinder , Sawhney Amrita , Gorritz Magdaliz , Chen Chi-Chang , Paltanwale Queenie , Sun Kainan , Shore Neal D. 
Published: January 2024

81 Background: In March 2022, the US Food and Drug Administration approved 177Lu-PSMA-617 for the treatment of patients with prostate-specific membrane antigen (PSMA) positive metastatic castration resistant prostate cancer (mCRPC) who have been treated with androgen receptor pathway inhibition (ARPI) and taxane-based chemotherapy. This real-world study aims to describe clinical characteristics, treatment use, clinical outcomes in patients treated with 177Lu-PSMA-617 in a growing US dataset. Methods: Adults (≥18 years) with ≥1 claim for 177Lu-PSMA-617 between 3/01/22 and 6/30/2023 in the IQVIA open-source pharmacy and medical claims databases were retrospectively identified and included in this analysis. Clinical characteristics and treatment use, including prior treatment exposures, were derived from this cohort. A subset of these patients with available PSA results were assessed for PSA response after initiation of 177Lu-PSMA-617. Baseline PSA was defined as the closest PSA value within 90 days prior to or on the first 177Lu-PSMA-617 claim (index date). Post-treatment PSA response was defined as the lowest PSA value ≥28 days after the index date. The proportion of patients with ≥ 50%, ≥80% and ≥90% PSA reductions were reported. Results: A total of 1,710 patients treated with 177Lu-PSMA-617, with mean (standard deviation) age was 72.2 (8.5) years, met eligibility and were included in the study. Common comorbidities included hypertension (34.7%), osteoarthritis (27.3%) and dyslipidemia (23.9%). Based on ICD-10 codes, 1,447 (84.6%) patients had bone metastases, and 575 (33.6%) had visceral metastases, of whom 128 (7.5%) had liver metastases. Only 59 (3.5%) patients had lymph node only metastasis. In the pre-index period, 83.4% patients had used prior ARPI and/or taxane chemotherapy, and 98% patients had used other systemic therapies. In a sub-analysis of 159 (9.3%) patients with pre- and post-index PSA values available (whose clinical characteristics are comparable to the overall cohort of 1,710 patients), median PSA at baseline before initiation of 177Lu-PSMA-617 was 61 ng/ml. Among these patients, 53.5%, 29.6% and 22.6% had PSA reductions of ≥50%, ≥80% and ≥90%, respectively, while on treatment. Rate of PSA response was similar regardless of history of ARPI or taxane use. Conclusions: To our knowledge, this is the first large-scale report of real-world US patients treated with 177Lu-PSMA-617. Clinical characteristics and PSA responses observed are consistent with results from the VISION clinical trial demonstrating benefit with 177Lu-PSMA-617 treatment. Subsequent analysis with longer follow up are needed to understand the long-term outcomes associated with 177Lu-PSMA-617 in real-world US patients.
Real-world clinical outcomes of patients treated with Lu-177-PSMA-617 for metastatic castration-resistant prostate cancer (mCRPC): A single-institution experience.
Authors: Maldonado Grijalva Valeria , Wang John , Nedrud Marybeth , Kelleher Colm , Wong Terence Z. , Labriola Matthew , McManus Hannah Dzimitrowicz 
Published: January 2024

83 Background: The radiopharmaceutical Lu177-PSMA-617 (LuPSMA) was FDA approved in March 2022 for patients with mCRPC previously treated with both an androgen receptor signaling inhibitor (ARSI) and a taxane, if eligible based on PSMA PET. However, data regarding real world LuPSMA treatment outcomes are limited. Methods: This is a retrospective analysis of the first 100 mCRPC patients who received at least 1 cycle of LuPSMA at a single institution from June 2022 to August 2023. Demographic and clinical characteristics as well as laboratory values were collected. Central review of qualifying PSMA PET/CT was performed to assess disease distribution. A PSA decrease of 30%, 50%, or 90% from baseline at any point during treatment was the primary measure of response (PSA30, PSA50, and PSA90 respectively). Results: Of the 100 patients identified, 2 were excluded from analysis due to prior receipt of LuPSMA on clinical trial. Three patients were still receiving LuPSMA at the time of data collection. Median age was 72 (range, 50 - 93) and median number of treatments received was 4.0. On baseline PET/CT, 43 patients (44%) had bone + nodal metastases only, 19 (19%) had bone metastases only, 8 (8%) had nodal metastases only, and 11 (11%) had liver metastases. As for prior therapies, 47% had received ≥2 ARSIs (n=47/98), 48% had received 2 prior taxanes (n= 47/98), 42% had received 1 prior taxane (n=41/98), 17% received radium-223 (n=17/98), and 10% were treated off-label with no prior chemotherapy (n=10/98). Median follow up from the start of LuPSMA treatment was 7.6 months (range= 0.6-14.1 months, n=98). During treatment, 21 (21%) patients achieved a PSA90 response, 51 (52%) patients achieved a PSA50 response and 60 (61%) patients achieved a PSA30 response. An increase or no change in baseline PSA was seen in 28% (n=26/94 evaluable patients). Among patients with an initial rise in PSA after the first treatment, 10% had a subsequent reduction from baseline PSA (n=3/29). Conclusions: In this cohort of heavily pretreated mCRPC patients, we observed a PSA50 response of 54% and 21% of patients experiencing a PSA reduction ≥90%. This data supports the clinical benefit of LuPSMA in real-world clinical practice. Characterization of response rates within subgroups by prior treatment and disease characteristics are ongoing.
Subcutaneous nivolumab (NIVO SC) vs intravenous nivolumab (NIVO IV) in patients with previously treated advanced or metastatic clear cell renal cell carcinoma (ccRCC): Pharmacokinetics (PK), efficacy, and safety results from CheckMate 67T.
Authors: George Saby , Bourlon Maria Teresa , Chacon Matias Rodrigo , Cutuli Hernan , Lopez Chuken Yamil Alonso , Zurawski Bogdan , Mota Jose Mauricio , Magri Ignacio , Burotto Mauricio , Luz Murilo , De Menezes Juliana , Yanez Ruiz Eduardo Patricio , Maruzzo Marco , Bracarda Sergio , Prusty Subhransu , Rathod Dhanrajsinh , Vezina Heather , Yu Zhuoxin , Zhao Yue , Albiges Laurence 
Published: January 2024

LBA360 Background: NIVO IV has improved outcomes in multiple tumor types. Evolving treatment paradigms have created a need for administration options that address treatment burden and improve efficiencies of healthcare systems. SC delivery of antibodies for various cancer indications has proved safe and effective. CheckMate 67T (NCT04810078) is a multicenter, randomized, open-label, phase 3 study that evaluated PK and objective response rate (ORR) noninferiority of NIVO SC vs IV in patients (pts) with locally advanced or metastatic ccRCC. Methods: Enrolled pts had measurable disease that progressed during or after 1–2 prior systemic regimens, no prior immuno-oncology treatment, and a Karnofsky performance score ≥ 70. Pts were randomized 1:1 to receive NIVO SC 1200 mg + recombinant human hyaluronidase PH20 Q4W or NIVO IV 3 mg/kg Q2W until disease progression, unacceptable toxicity, withdrawal of consent, completion of 2 years’ treatment, or death. The co-primary PK endpoints for noninferiority testing were time-averaged serum concentration over the first 28 days (Cavgd28) and minimum serum concentration at steady state (Cminss) determined by a population PK analysis. ORR by blinded independent central review (BICR) was a key powered secondary endpoint for noninferiority testing. Other secondary objectives included additional PK exposure measures, safety, efficacy, and immunogenicity. Results: A total of 495 pts were randomized to NIVO SC (n = 248) or NIVO IV (n = 247). The median age was 64/66 years in the SC/IV arms. Most pts were male. Average injection time with NIVO SC was < 5 minutes. Noninferiority for the co-primary PK and key powered secondary ORR endpoints was met (see table). Incidence of NIVO SC local injection-site reactions was 8.1%; reactions were low grade and transient. Most deaths were due to disease progression; study drug toxicity led to 3/1 deaths with NIVO SC/IV. Conclusions: The co-primary PK and key powered secondary ORR endpoints were met, supporting the use of NIVO SC as a new option to improve healthcare efficiency. The safety profile for NIVO SC was consistent with NIVO IV. Clinical trial information: NCT04810078 .[Table: see text]
ARAMON: A phase 2, randomized, open-label study comparing darolutamide (DARO) vs enzalutamide (ENZA) monotherapy on serum testosterone levels in patients (pts) with castration-sensitive prostate cancer (CSPC) after biochemical recurrence (BCR).
Authors: Laccetti Andrew Leonard , Smith Matthew Raymond , Scher Howard I. , Verholen Frank , Adorjan Patrick , Dissanayake Manjari , Gao Xin 
Published: January 2024

TPS243 Background: DARO, a structurally distinct and highly potent androgen receptor inhibitor, has low blood–brain barrier (BBB) penetration and limited potential for drug–drug interactions. In phase 3 trials, DARO showed significant efficacy and a favorable safety profile. In ARAMIS (NCT02200614), DARO and androgen-deprivation therapy (ADT) significantly improved metastasis-free survival and overall survival (OS) vs placebo + ADT in pts with nonmetastatic castration-resistant prostate cancer. In ARASENS (NCT02799602), DARO + ADT + docetaxel significantly improved OS in pts with metastatic hormone-sensitive prostate cancer vs placebo + ADT + docetaxel. In both studies, the incidence of adverse events (AEs) was similar between treatment groups. Currently, the ARASTEP study (NCT05794906) is evaluating DARO and ADT in pts with high-risk BCR following primary therapy who have prostate-specific membrane antigen PET/CT-positive lesions. Based on a neuroimaging study of healthy volunteers, cerebral blood flow was not altered with DARO but was significantly reduced in brain areas related to cognition with ENZA. It is postulated that the low BBB penetration of DARO may result in lower serum testosterone elevations than those seen with ENZA, which may reduce the frequency of AEs. The ARAMON study (NCT05526248) will compare the effect of DARO and ENZA monotherapy on post-treatment testosterone levels in pts with CSPC who developed a BCR after definitive treatment for localized disease. Methods: ARAMON is a two-stage, open-label, phase 2 study of pts with histologically or cytologically confirmed adenocarcinoma of the prostate who experienced BCR after radical primary prostatectomy (RP) or radiation therapy (RT), with <5 asymptomatic oligometastatic disease sites. Key inclusion criteria are prostate-specific antigen (PSA) ≥2 ng/mL, PSA doubling time of ≤20 months, serum testosterone >150 ng/dL, and Eastern Cooperative Oncology Group performance status 0/1. During the lead-in phase, 25 pts will receive DARO 600 mg twice daily for 52 weeks. If serum testosterone criteria are met at 12 weeks, the study will proceed to the randomized phase where approximately 40 pts will be randomized 1:1 to DARO (600 mg twice daily) or ENZA (160 mg once daily) for 52 weeks. The primary endpoint is the change in serum testosterone level from baseline to Week 12. Secondary endpoints include the change in serum testosterone levels from baseline to Weeks 24 and 52; PSA at Weeks 4, 12, 24, 36, and 52; changes in blood levels of endocrine, glycemic, and lipid metabolism markers; incidence of AEs; and quality of life. As of September 2023, 23 of 25 planned pts in the lead-in phase have been enrolled. Clinical trial information: NCT05526248 .
Darolutamide plus androgen-deprivation therapy (ADT) in patients with high-risk biochemical recurrence (BCR) of prostate cancer: A phase 3, randomized, double-blind, placebo-controlled study (ARASTEP).
Authors: Chehrazi-Raffle Alex , Morgans Alicia K. , Gschwend Jürgen E. , Shore Neal D. , Ross Ashley , Feng Felix Y , Hope Thomas A. , Trandafir Lucia , Kuss Iris , Le Berre Marie-Aude , Joensuu Heikki , Fizazi Karim 
Published: January 2024

TPS254 Background: Patients with prostate cancer treated with radiotherapy (RT) or radical prostatectomy (RP) as primary therapy may develop BCR, defined as a prostate-specific antigen (PSA) increase without evidence of metastases on conventional imaging. Prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT), a more effective and precise imaging method, may detect small lesions in patients with BCR. Patients with BCR at high risk of metastatic progression and who have lesions identified by PSMA PET/CT need effective treatment to delay this progression. Darolutamide (DARO) is a structurally distinct and highly potent androgen receptor inhibitor, which significantly improved metastasis-free survival (MFS) and overall survival (OS) in patients with nonmetastatic castration-resistant prostate cancer (nmCRPC). The ARASTEP study (NCT05794906) is designed to evaluate whether DARO plus ADT improves radiological progression-free survival (rPFS) by PSMA PET/CT vs placebo (PBO) plus ADT in patients with BCR following primary therapy and PSMA PET/CT-positive lesions. Methods: Eligible patients must have prostate cancer treated by primary RT or RP followed by adjuvant RT (ART) or salvage RT (SRT), or RP alone if ART/SRT was not appropriate, with high-risk BCR (defined as PSA doubling time [PSADT] <12 months and PSA ≥0.2 ng/mL after primary RP [± ART/SRT] or PSA ≥2 ng/mL above nadir after primary RT only), ≥1 PSMA PET/CT-positive lesion of prostate cancer without visible lesions on conventional imaging, and serum testosterone >150 ng/dL. Approximately 750 patients from 184 sites worldwide will be randomized to oral DARO 600 mg twice daily or PBO, both with ADT, for 24 months unless, during this period, there is disease progression, unacceptable toxicity, or any other withdrawal criteria are met. Patients will suspend treatment after 24 months if PSA values are undetectable (<0.2 ng/mL). Patients whose PSA values are still detectable (≥0.2 ng/mL) will continue with the study treatment until PSMA PET/CT progression. Image-guided radiotherapy or surgery is allowed within 12 weeks from randomization. Randomization is stratified by PSADT <6 vs ≥6–<12 months, intent to treat baseline PSMA PET/CT lesions with image-guided radiotherapy/surgery (Yes vs No) and distant ± locoregional vs locoregional-only metastases. The primary endpoint is rPFS by PSMA PET/CT, assessed by blinded independent central review (BICR). Secondary endpoints include MFS by BICR, time to CRPC, OS, quality of life, and safety. As of September 2023, 1 patient has been enrolled. Clinical trial information: NCT05794906 .