bluuebunny/crossref_metadata_2025_split huggingface dataset:
Real-world combination therapy patterns in patients receiving leuprolide or relugolix for androgen deprivation therapy in 2021 (The REAL-ADT COMBO Study): Analysis from a US EMR database.
Authors: McKay Rana R. , Gandhi Raj , Yang Eric , Pruett Janis , Nwokeji Esmond , Fallick Mark 
Published: March 2023

74 Background: Relugolix, an oral gonadotropin releasing hormone (GnRH) receptor antagonist, was FDA approved for the treatment of adults with advanced prostate cancer (PC) in December 2020 and became commercially available in January 2021. Data from a subgroup of patients from the Phase 3 HERO study showed patients combining relugolix with enzalutamide or docetaxel had similar efficacy and safety as other cohorts in the study. However, due to limited data, some guidelines do not recommend relugolix in combination with other therapies. We evaluated real world utilization of leuprolide and relugolix in combination with other PC medications. Methods: An observational retrospective analysis was conducted using Electronic Medical Record (EMR) data. PPS Analytics data from 89 urology practices with patients represented across all 50 states in the US were analyzed. Patients with at least one record of androgen deprivation therapy (ADT) in 2021 were included. Patients whose date of ADT initiation could not be determined were excluded from this analysis. This analysis focused on the occurrence of patients with ADT as well as in combination with other PC medications. Data are reported for all patients treated with leuprolide or relugolix and stratified by new and continuing ADT use. Combination PC medications were reported for these two ADT groups. Results: In 2021, 51,735 patients were treated with ADT; 45,599 (88.1%) were treated with leuprolide and 3,096 (6.0%) patients had at least 1 prescription for relugolix. Combination PC medications (ComboPCRx) were proportionately higher in relugolix patients than in leuprolide patients (698 [22.5%] vs 8,897 [19.5%] respectively; p < 0.0001). ComboPCRx in users new to ADT was more frequent for relugolix users (342/2,169 [15.8%]) than for leuprolide users (1934/17,737 [10.9%]). In both groups, novel anti-androgens were the most frequent type of ComboPCRx. Conclusions: In this real-world EMR analysis, relugolix use in combination with other PC medication was frequently observed, for both new to ADT and continuing ADT patients. The percentage of combination therapy with PC medications was higher for relugolix users than it was for leuprolide users. These results provide insight into the real-world use of relugolix in combination with other PC medications. Further analyses are needed to make informed treatment decisions. [Table: see text]
Activity and tolerability of maintenance avelumab (AVE) immunotherapy after first-line platinum-based polychemotherapy in patients (pts) with locally advanced or metastatic squamous cell penile carcinoma: Initial results of PULSE study.
Authors: Thiery-Vuillemin Antoine , Tartas Sophie , Mourey Loic , Colomba Emeline , Borchiellini Delphine , Goujon Morgan , Lefort Felix , Topart Delphine , Barthelemy Philippe , Lauridant Geraldine , Meurisse Aurelia , Vernerey Dewi , Massard Vincent 
Published: March 2023

8 Background: Metastatic squamous cell penile carcinoma (mSCPC) is an orphan disease with a virally induced oncogenesis. PD-L1 expression rate is around 60% with a strong correlation between PD-L1 in the primary tumour and metastases. The first line systemic treatment relies on platinum-based chemotherapies with a median progression free survival and overall survival around 7.5 and 16 months (mo), respectively. Immunotherapies targeting PD-1/PD-L1 axis are effective in other squamous cell or HPV related cancers. Methods: PULSE is a national prospective multicenter open label single arm phase II trial. Thirty-two pts will be enrolled after a radiological assessment showing a non-progressive disease after 3 to 6 cycles of a first line platinum-based polychemotherapy. Pts will receive AVE injections 10mg/kg every two weeks until progression or unacceptable toxicity. The primary endpoint will be the progression free survival (PFS) from AVE initiation according to RECIST v1.1 criteria. Key secondary endpoints will include, overall survival, safety. Here we report the results of the first interim analysis (IA). Results: From September 2019 to October 2022, 14 pts has been enrolled. Within the 9 first patients involved for the IA the median age was 69.9 years; 89% of pts had an ECOG 0-1. Of them, 1 patient and 8 pts had stage 3 and 4 disease at chemotherapy initiation, respectively. Median follow-up was 5.8 [2.3-17.2] mo. Chemotherapy regimens were triplets for 5 pts (56%), containing cisplatin for 56% and a taxane for all pts. Median duration of chemotherapy was 3.7 mo [1.2; 11.7]. At AVE initiation, 5 pts (56%) had partial or complete response and 4 pts (44%) had stable disease. Median duration of AVE was 3.7 mo with a majority (83%) of discontinuation linked to disease progression. Survival data are shown in the table. No new safety signal was identified. Conclusions: PULSE is the first prospective trial exploring avelumab maintenance activity in mSCPC. After the IA the DSMB have recommended to pursue the study based on these promising results. Updated results with additional patients, longer follow-up and ancillary explorations with biomarkers analysis will be presented at the meeting. Clinical trial information: NCT03774901 . [Table: see text]
Oncologists’ perspectives on metastatic hormone sensitive prostate cancer management.
Authors: Heckman Patrick , Yan Donglin , Zhou Xitong , Myint Zin 
Published: March 2023

84 Background: The treatment of metastatic hormone sensitive prostate cancer (mHSPC) has evolved over the past 7 years. Combination therapies with either [Androgen deprivation therapy (ADT) + Docetaxel] or [ADT + androgen receptor signaling inhibitors (ARSi) such as abiraterone acetate/enzalutamide/apalutamide] have demonstrated overall survival (OS) benefit compared to ADT + placebo in mHSPC. Recently two trials (ARASENS and PEACE-1) also demonstrate an OS benefit from the addition of docetaxel to ADT + ARSi (abiraterone acetate or darolutamide) compared to ADT + docetaxel. Given these recent advances there is not a clear consensus on how to best manage patients with mHSPC as there are no head-to-head trials. In this study, we assess oncologists’ treatment preferences as it pertains to this subset of patients. Methods: An 8-item online survey was sent on September 6th, 2022 to medical oncologists in the United States. We described five different case scenarios and three demographic questionnaires. Cases consisted of patients with mHSPC both de novo and primary progressive with low and high volumes. Treatment options included ADT monotherapy, ADT + ARSi (doublet), or ADT + ARSi + docetaxel (triplet therapy). Respondents reported their practice setting, location, and years of clinical experience. Data was collected and analyzed via REDCap. Results: Surveys were completed by (n=83) medical oncologists across the US. 14.5% of respondents were from Kentucky; 51.8% have been in practice < 10 years, 20.5% 10-20 years, and 27.7%> 20 years. For patients with de novo high volume disease, 85.5% (71) preferred treatment with triplet therapy. For the same patient population, 94.4% (51) of university-based providers preferred triplet therapy vs 68.9% (20) of those in a non-academic setting. Preferences differed regarding patients with primary progressive high-volume disease in which 59.8% (49) preferred a triplet regimen while 37.8% (31) preferred a doublet regimen. Of those choosing triplet therapy, 53.7% (29) were from an academic institution while 71.4% (20) practiced in a nonacademic setting. Of those choosing doublet therapy, 42.6% (23) were from an academic institution versus 28.6% (8) in a nonacademic setting. For patients with de novo or primary progressive low volume disease, 81.5% of respondents preferred doublet therapy without a notable difference between academic and non-academic responders. Conclusions: We find a consensus in management of patients with de novo high volume mHSPC (prefer triplet) and de novo or primary progressive low volume disease (prefer doublet) regardless of practice setting, location, or practice duration. However, for patients with primary progressive high-volume disease, a higher percentage of non-academic providers prefer triplet therapy compared to their university counterparts.
Physician preferences for nonmetastatic castration-resistant prostate cancer treatments: A discrete choice experiment among men in mainland China.
Authors: Fan Yu , Huang Shiyun , Xu Rui , He Zhisong 
Published: March 2023

88 Background: A range of medication options are available for non-metastatic castration-resistant prostate cancer (nmCRPC), with varying efficacy and safety profiles. We used a discrete choice experiment (DCE) to explore how physicians make treatment decisions between adverse events (AEs) and survival gains in nmCRPC in mainland China. Methods: Physicians’ preferences for medication attributes were assessed through an online survey including 14 treatment choice questions, each comparing 2 hypothetical treatment profiles, which varied safety (fatigue, skin rash, cognitive problems, falls, and fractures) in terms of severity and frequency and efficacy (overall survival [OS] and time to pain progression [TPP]) in terms of duration of effect. Preference weights and importance scores for each attribute were estimated using random parameters logit models. The amount of survival gain physicians were willing to trade off for a reduction in specific AEs was also estimated. Results: In total, 80 physicians who had experience in treating nmCRPC patients were involved in this study. Physicians’ duration of clinical practice was about 18.4±7.39 years. In addition, 57.6% of participants were from regions with more developed economics, including North, East and South China. The results indicated that physician preferences were logically ordered, with higher efficacy and lower risks for AEs being favored over lower efficacy and higher risks for AEs. The most important attributes for treatment decision were OS (Relative importance, RI = 29.2%), serious fracture (RI = 24.4%), serious fall (RI =15.4%) and TPP (RI =10.6%). Comparing non-serious AEs including fatigue, skin rash and cognitive problems, physicians emphasized the risk reduction of fatigue the most. The trade-off analysis between OS and adverse events suggested that physicians were willing to trade 7.5 and 4.7 months of OS to reduce the risk of severe fracture from 8% to none, and the risk of serious fall from 8% to none. In an exploratory subgroup analysis, it was found that physicians with more than 15 years of clinical practice put more emphasis on overall survival, risk of serious fracture, and risk of serious fall compared to less experienced physicians (≤15 years). Physicians from regions with more developed economics tended to put more value on reduction of AEs as compared to physicians from the rest regions. Conclusions: OS is the most important attribute for physicians when treating nmCRPC patients. Physicians were willing to trade the duration of OS to reduce the risk of serious adverse events. These results emphasize the importance of carefully balancing therapies’ benefits and risks to ultimately optimize the overall quality of nmCRPC patients’ survival.
Atezolizumab (atezo) + platinum/gemcitabine (plt/gem) vs placebo + plt/gem for first-line (1L) treatment (tx) of locally advanced or metastatic urothelial carcinoma (mUC): Final OS from the randomized Phase 3 IMvigor130 study.
Authors: Galsky Matt D. , Arranz Arija Jose Angel , De Santis Maria , Davis Ian D. , Bamias Aristotelis , Kikuchi Eiji , Garcia del Muro Xavier , Park Se Hoon , De Giorgi Ugo , Alekseev Boris , Mencinger Marina , Izumi Kouji , Puente Javier , Li Jian-Ri , O'Donnell Peter H. , Bernhard Sandrine , Lee Chooi Peng , Bene-Tchaleu Fabiola , Mariathasan Sanjeev , Grande Enrique 
Published: March 2023

LBA440 Background: The IMvigor130 primary analysis demonstrated statistically significant PFS benefit with 1L atezo + plt/gem (Arm A) vs placebo + plt/gem (Arm C) in pts with mUC (Galsky Lancet 2020). Interim data showed improved OS with Arm A vs C but did not cross the pre-specified threshold for significance (Galsky Lancet 2020; Galsky AACR 2021). In exploratory analyses, OS improved when atezo was combined with cisplatin (cis) vs carboplatin (carbo) regardless of PD-L1 status. Here, we report final OS data from Arms A and C. Methods: Pts were randomly assigned 1:1:1 to Arm A, B (atezo alone) or C. Arm A and C pts received cis or carbo per investigator (INV) choice. Co-primary endpoints were PFS per INV RECIST 1.1 and OS (Arm A vs C), and OS (Arm B vs C), tested hierarchically. Safety, ORR and DOR, disease control rate (DCR; confirmed CR, PR or [SD ≥ 6 mo]) and pre-specified exploratory OS data are also reported. Results: As of data cutoff Aug 31, 2022 (49 mo since last pt randomly assigned), in ITT pts, OS benefit was not statistically significant; in the cis subgroup, HR was 0.76 (95% CI 0.57, 1.01; Table). In ITT pts, DCR was 65% (290/447) in Arm A and 60% (239/397) in Arm C. 81% of safety-evaluable pts (370/454) in Arm A and 80% (312/389) in Arm C had a Gr 3/4 tx-related AE (TRAE). Gr 5 TRAEs occurred in 9 pts (2%) in Arm A and 4 (1%) in Arm C; Gr 3/4 AEs of special interest were seen in 41 pts (9%) in Arm A and 17 (4%) in Arm C. Conclusions: In this final analysis, improved OS with atezo + plt/gem vs placebo + plt/gem did not reach statistical significance in ITT pts with mUC. As seen with prior exploratory data, improved OS with atezo + plt/gem was greater when pts received cis vs carbo. No new safety signals were seen. Clinical trial information: NCT02807636 . [Table: see text]
Extreme bipolar androgen therapy with darolutamide and testosterone cypionate in patients with metastatic castration-resistant prostate cancer: ExBAT (LACOG 0620) trial.
Authors: Isaacsson Velho Pedro H , Girardi Daniel da Motta , Soares Andrey , Fontes Jardim Denis Leonardo , Maluf Fernando Cotait , Morbeck Igor Alexandre , Dias Mariane Fontes , Souza Vinicius Carrera , Silva Adriano Goncalves E , de Jesus Rafaela Gomes , Rebelatto Taiane Francieli , Bastos Diogo Assed 
Published: March 2023

TPS276 Background: Prostate cancer has an intrinsic dependence on androgens and androgen receptor (AR) regulation. Suppression of gonadal androgen synthesis known as androgen deprivation therapy (ADT), either by orchiectomy or by pharmacological modulation, represents the treatment backbone of metastatic disease. Unfortunately, almost invariably, patients develop resistance to ADT, progressing to a state called castration-resistant prostate cancer (CRPC), defined as disease progression at serum testosterone levels in the castrate range. Bipolar Androgen Therapy (BAT), consisting of exogenous supraphysiological doses of testosterone followed by castrate levels, has shown clinical activity in multiple early phase clinical trials, in addition to improvement of quality of life (QoL) in CRPC patients. Alternated administration of BAT and novel AR-targeted therapies, a strategy entitled by our group as Extreme Bipolar Androgen Therapy (ExBAT), has never been tested in patients with CRPC. The objective of our study is to assess the ExBAT approach in metastatic CRPC. Methods: ExBAT (NCT04558866) is a phase 2, single-arm, multicenter trial assessing patients with mCRPC who progressed to abiraterone by PCWG3 criteria. Prior docetaxel for metastatic hormone-sensitive disease is allowed if ≥ 12 months elapsed from last dose of docetaxel. Included patients receive testosterone cypionate 400 mg IM on day 1 followed by darolutamide 1,200 mg/day orally for 4 weeks (starting on day 29 through day 56) on 63-day cycles. The primary endpoint is radiographic progression-free survival (rPFS) at 12 months. Secondary endpoints include PSA decline rates, overall survival, toxicity, quality of life, and predictive biomarkers of response/survival. Tumor assessments are performed every 9 weeks, for the first 2 cycles and every 18 weeks thereafter up to 12 months. Patients with disease progression with clinical benefit are allowed to continue treatment. Patients without disease progression after 12 months are allowed to receive study treatment on Extension Phase. The sample size of 47 patients (considering 5% drop-out) was calculated based on the primary endpoint using a two-sided 5% significance level Chi-square Test for One Proportion and achieves 80% power to detect the difference between a 50% rPFS at 12 months comparing with 30% in the historic control group. NCT04558866. From June2021 to September2022, 31 of planned 47 patients have been enrolled in 8 Brazilian centers. Results are not available at the time of submission. Clinical trial information: NCT04558866 .
A phase 1/2 study of REGN4336, a PSMAxCD3 bispecific antibody, alone and in combination with cemiplimab in patients with metastatic castration-resistant prostate cancer.
Authors: Kelly William Kevin , Hussain Arif , Saraiya Biren , Thanigaimani Pradeep , Sun Furong , Seebach Frank A. , Lowy Israel , Sandigursky Sabina , Miller Elizabeth 
Published: March 2023

TPS284 Background: Prostate cancer is the leading cause of new cancer diagnoses and the second most common cause of cancer-related death in American men. Prognosis is especially poor for men with metastatic castration resistant prostate cancer (mCRPC). Prostate-specific membrane antigen (PSMA) is highly expressed on malignant prostate tissue but shows limited expression on normal tissue. As such, PSMA is an excellent research target for treatment of mCRPC. REGN4336 is a PSMAxCD3 bispecific antibody designed to facilitate T-cell–mediated killing of PSMA-expressing tumor cells. In preclinical models, REGN4336 demonstrated strong PSMA-dependent antitumor activity that was dose-dependent. Preclinical data also support clinical research into the combination of REGN4336 with cemiplimab (anti–programmed cell death-1) for treating mCRPC. Methods: This is an open-label, Phase 1/2, first-in-human, multicenter dose-escalation study with dose expansion evaluating safety, tolerability, pharmacokinetics (PK), and antitumor activity of REGN4336 administered subcutaneously alone and in combination with intravenous cemiplimab in patients with mCRPC (NCT05125016). Patients must have received at least two prior lines of systemic therapy approved for metastatic and/or castration-resistant disease including a second-generation anti-androgen therapy. In Module 1, REGN4336 as monotherapy is administered weekly but may be extended to once every 3 weeks following identification of the minimal pharmacologically active dose. In Module 2, REGN4336 will be administered in combination with cemiplimab (350 mg) once every 3 weeks after a 4-week REGN4336 monotherapy lead-in cycle. Study therapies are administered until disease progression, intolerable adverse events, withdrawal of consent, or a study withdrawal criterion is met. The primary objectives in dose escalation are to evaluate the safety, tolerability, PK, and recommended phase 2 dosing regimen (RP2DR) of REGN4336 alone and in-combination with cemiplimab. Expansion cohort(s) will be enrolled once RP2DRs have been determined. During the expansion phase, the primary objective is to assess clinical activity, as measured by objective response rate with REGN4336 alone or in combination with cemiplimab per modified Prostate Cancer Working Group 3 criteria. At selected sites, PSMA positron emission tomography/computed tomography scans will be performed at predefined timepoints on study. This study is currently open to enrollment. Clinical trial information: NCT03088540 .
SunRISe-4: TAR-200 plus cetrelimab or cetrelimab alone as neoadjuvant therapy in patients with muscle-invasive bladder cancer (MIBC) who are ineligible for or refuse neoadjuvant platinum-based chemotherapy.
Authors: Psutka Sarah P. , Cutie Christopher , Bhanvadia Sumeet Kaur , Keegan Kirk A. , Crist Wendy , Tian Shaozhou Ken , Maffeo John , Raybold Bradley , Kashmer Marietta , Hasan Mohamad , Li Xiang , Beeharry Neil , Thomas Shibu , Tian Hui , Powles Thomas 
Published: March 2023

TPS584 Background: Standard of care for patients (pts) with MIBC is radical cystectomy (RC) with neoadjuvant systemic platinum-based chemotherapy (PBC); however, systemic chemotherapy is associated with significant toxicity. TAR-200 is an intravesical drug delivery system that provides local continuous gemcitabine release within the bladder. SunRISe-4 (NCT04919512) is an open-label, multicenter, randomized phase 2 study designed to assess the efficacy and safety of neoadjuvant TAR-200 + systemic cetrelimab (CET [anti–programmed death-1 antibody]) vs neoadjuvant CET alone in pts with MIBC scheduled for RC who are ineligible for or refuse neoadjuvant PBC. Methods: Eligibility criteria: age ≥18 years, Eastern Cooperative Oncology Group performance status of 0 or 1, histologically confirmed cT2-T4a MIBC with absence of nodal or metastatic disease at screening, and residual intravesical tumor volume of ≤3 cm prior to randomization. Pts will be stratified by completeness of transurethral resection of bladder tumor (TURBT; visibly complete vs incomplete and ≤3 cm) and tumor stage (cT2 vs cT3-4a) at initial diagnosis. Pts (N≈160) will be randomized 5:3 to receive TAR-200 + CET (Cohort 1, n≈100) or CET alone (Cohort 2, n≈60). In Cohort 1, TAR-200 (225 mg gemcitabine) will be placed intravesically at the initial treatment visit; TAR-200 will be removed and replaced over a 12-week period. In both cohorts, CET will be serially dosed intravenously over the same timeframe. Primary disease assessments include axial imaging (at screening and Week 6), centralized review of TURBT (initial diagnostic TURBT or debulking TURBT for pts with lesions >3 cm after initial TURBT) as well as RC and nodal tissue specimens. After RC, all pts will have follow-up visits from Weeks 4 to 108 post RC (end of study). The primary outcome measure is the pathologic complete response rate at time of RC. Secondary outcome measures include safety, tolerability, and recurrence-free survival (per Response Evaluation Criteria in Solid Tumors 1.1 or histologic evidence). Exploratory outcome measures include patient-reported cancer-related quality of life (Functional Assessment of Cancer Therapy–Bladder questionnaire) and pathologic overall response rate at RC. Overall survival and time to symptomatic progression, pharmacokinetics, biomarker analysis, and immunogenicity will also be evaluated. As of September 12, 2022, 2 of 160 planned pts have been enrolled and randomized, and recruitment is ongoing at ≈95 sites. Clinical trial information: NCT04919512 .