bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic implications of PSA levels at 7 months in metastatic hormone-sensitive prostate cancer treated with enzalutamide: Landmark analysis of ENZAMET (ANZUP 1304).
Authors: Mc Laughlin Ronan Andrew , Thomas Hayley , Davis Ian D. , Zielinski Robert Richard , Thomson Alastair , Tan Thean Hsiang , Sandhu Shahneen , Reaume M. Neil , Pook David William , Parnis Francis , North Scott A. , Marx Gavin M. , McCaffrey John , McDermott Raymond S. , Horvath Lisa , Frydenberg Mark , Chowdhury Simon , Chi Kim N. , Stockler Martin R. , Sweeney Christopher ,   Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP)
Published: June 2024

5079 Background: ENZAMET (NCT02446405) showed that enzalutamide added to testosterone suppression (TS) with or without docetaxel improves overall survival (OS) compared with TS plus standard non-steroidal anti-androgen (NSAA) in patients with metastatic hormone-sensitive prostate cancer (mHSPC). We assessed PSA levels in ENZAMET participants at 7 months after randomization to determine correlations with OS. In CHAARTED, participants with mHSPC high volume disease (HV), 20% achieved PSA ≤ 0.2 with ADT (androgen deprivation therapy) alone versus 44% with low volume disease (LV) and for HV with ADT + Docetaxel, 36% achieved PSA ≤ 0.2 vs 64% with LV. Methods: Participants were included if they were followed for at least 7 months after randomization, and had availability of PSA and outcome data. Landmark analysis at 7 months used prognostic classifiers as previously identified in SWOG 9346 and CHAARTED of PSA ≤ 0.2 and > 0.2 at 7 months after initiation of therapy. Results: The total number of ENZAMET participants (pts) with PSA at 7 months of ≤0.2ng/mL was 646 of 1125 (57%): 271/562 (48%) in the NSAA arm versus 375/563 (67%) in the ENZA arm. Five-year OS for TS + NSAA (±Doc) arm PSA ≤ 0.2 = 71% vs PSA > 0.2 = 36% and for TS + ENZA (±Doc) arm PSA ≤ 0.2 = 74% vs PSA > 0.2 = 43%. The % of pts with PSA levels at 7 months ≤0.2ng/mL and corresponding 5-year OS outcomes by key prognostic groups (HV vs LV) ± docetaxel is shown (Table). In comparison with CHAARTED in those with HV, 37% achieved PSA ≤ 0.2 with ADT alone versus 61% with LV which increased to 55% for HV and 79% for LV respectively with addition of enzalutamide. In those with HV treated with ADT + D 39% achieved PSA ≤ 0.2 vs 58% with LV increasing to 60% for HV and 74% for LV respectively with addition of enzalutamide. Conclusions: A PSA nadir of ≤0.2 at 7 months is associated with a longer OS regardless of treatment and prognostic group (HV vs LV). Enzalutamide increased the rate of achievement of PSA <0.2 for all groups. Clinical trial information: NCT02446405 . [Table: see text]
Correlation of body mass index (BMI) with survival outcomes in patients (pts) with metastatic hormone-sensitive prostate cancer (mHSPC): Analysis of patient (pt)-level data from SWOG 1216 study.
Authors: Swami Umang , Jo Yeonjung , Narang Arshit , Plets Melissa , Hage Chehade Chadi , Gebrael Georges , Gupta Shilpa , Myint Zin , Tangen Catherine , Lara Primo N , Thompson Ian M. , Hussain Maha H. A. , Dorff Tanya B. , Lerner Seth P. , Agarwal Neeraj 
Published: June 2024

5081 Background: Obesity has been associated with improved survival outcomes in metastatic castration-resistant prostate cancer (PMID: 34226662). However, association of obesity with survival has not been reported in mHSPC setting. Herein we report the correlation of BMI with survival outcomes from patient level data from phase III study, SWOG 1216 which randomized pts with mHSPC in 1:1 to ADT + bicalutamide or ADT + orteronel. Methods: Inclusion: all pts treated on SWOG 1216 study with available BMI. Overall survival (OS) was summarized by median survival and its 95% confidence interval (CI). Multivariate analysis for OS was conducted using Cox proportional hazard model with categorized BMI as a continuous variable, and adjusted for treatment arm, disease burden, Gleason score, log 2 PSA, age and Zubrod performance status. All analysis was conducted using R v4.2.1. Results: Of 1279 pts, 12 were underweight, 252 had normal BMI, 958 were overweight and 57 were obese. Median age was 67.8 (IQR: 61.9, 73.9) years, no visceral metastases (88%) and baseline log2 median PSA of 4.89 (IQR: 3.27, 6.76). All four BMI cohorts had similar age, Gleason score, extensive disease burden, liver metastases and treatment allocation (p>0.05). Differences in baseline PSA and Zubrod performance status were observed between BMI cohorts (p<0.05). The OS (in years) in underweight, normal, overweight and obese cohorts was 1.8, 4.4, 6.5 and 4.8 for bicalutamide arm and 2.8, 5.7, not reached (NR) and NR for orteronel arm, respectively. After adjusting for prognostic variables, multivariate analysis confirmed that high BMI is associated with better OS (HR=0.82, 95% CI: 0.68-0.98; p=0.029) (Table). Conclusions: Our results show that as categorized BMI increased, the risk of death decreased in pts with mHSPC. These data warrant external validation in other randomized phase III studies and can help counseling and prognostication of patients with mHSPC in the clinic. Funding: NIH/NCI grants CA180888, CA180819, and in part by Millennium Pharmaceuticals (Takeda Oncology Company). Clinical trial information: NCT01809691 . [Table: see text]
Impact of alterations in tumor suppressor genes (TSG-alt) on survival outcomes in patients (pts) with de novo metastatic castration-sensitive prostate cancer (dn-mCSPC) receiving androgen deprivation therapy (ADT) with androgen receptor pathway inhibition (ARPI) or docetaxel.
Authors: Narang Arshit , Graf Ryon P , Gebrael Georges , Hage Chehade Chadi , Li Gerald , Ozay Zeynep Irem , Mazumder Archisman , Mathew Thomas Vinay , Maughan Benjamin L. , McKay Rana R. , Antonarakis Emmanuel S. , Swami Umang , Agarwal Neeraj 
Published: June 2024

5091 Background: TSG-alt have been associated with poor survival in the mCRPC setting (PMID: 31061129) and in the mCSPC setting from small single institution cohorts (PMID: 34294873). However, large studies evaluating their impact on survival outcomes with ADT intensification in mCSPC setting are lacking. Herein, we evaluate the impact of TSG-alt on outcomes in a large real-world patient population with dn-mCSPC receiving ADT treatment (Rx) with ARPI or docetaxel. Methods: This study used the nationwide (US-based) de-identified Flatiron Health-Foundation Medicine Prostate Cancer clinical-genomic database (FH-FMI CGDB), with de-identified data originating from approximately 800 US cancer clinics. Inclusion criteria: dn-mCSPC, tissue biopsy within 90 days of diagnosis, and initiation of ARPI or docetaxel + ADT within 120 days of diagnosis. Time to castration-resistance (TTCR) and overall survival (OS), indexed from metastatic diagnosis, were evaluated with Cox proportional hazards models adjusted for baseline prognostic factors (PSA, Gleason score, age, ECOG, hemoglobin, alkaline phosphatase, and albumin). OS risk intervals were left truncated to date of comprehensive genomic profiling report to adjust for immortal time bias. Results: Of 5356 pts in FH-FMI CGDB, 571 met inclusion criteria. Of these, 321 received ADT + ARPI and 250 ADT + docetaxel. Pts with pathogenic TSG alt were: 214 TP53 (37%), 154 PTEN (27%), and 37 RB1 (6%). Results are summarized in Table. Conclusions: In this real-world analysis, alt RB1 and alt TP53 had worse OS than their respective wild-type (wt) counterparts with both ARPI and docetaxel whereas alt PTEN had similar OS with ARPI and Docetaxel in dn-mCSPC pts. Based on these results, RB1 and TP53 may represent prognostic biomarkers guiding treatment selection and clinical trial enrollment in dn-mCSPC and may assist with counseling and prognostication. [Table: see text]
A phase 1/2 study of the TORC1/2 inhibitor onatasertib combined with toripalimab in patients with advanced solid tumors: Cervical cancer cohort.
Authors: Yuan Li , Shu Pei , Li Xiaoyu , Li Guiling , Zhang Keqiang , Lai Lin , Hong Jinsheng , Huang Chu-Ying , Wang Yongsheng , Xie Hui , Zheng Li , Zhou Qi 
Published: June 2024

5509 Background: Preliminary clinical data of oral TORC1/2 inhibitor, onatasertib (ATG-008), demonstrated anti-tumor activity and acceptable tolerability when combined with toripalimab (tori), an anti-PD-1 monoclonal antibody in solid tumors, especially in cervical cancer (CC). Here, we present results from the anti-PD1 naïve CC cohort of the TORCH-2 study who had at least prior 1 line of chemotherapy with the combination of onatasertib and tori. Methods: The TORCH-2 study is a phase 1/2 open-label, dose escalation and expansion trial of Onatasertib in combination with tori in patients (pts) with advanced solid tumours (NCT04337463). Eligibility criteria included at least one measurable lesion, ECOG 0-1 and adequate organ function. Pts with prior PI3K/AKT/mTOR inhibitor therapy were excluded, regardless of PD-L1 expression. Onatasertib was administered 15mg orally once a day (QD) in combination with tori 240 mg, once every 21 days (Q3W), which is the recommended phase 2 dose for the combination based on previous data. Efficacy assessments were reported based on RECIST1.1 criteria. Results: As of Oct 20, 2023, 31 checkpoint inhibitor (CPI) naïve advanced CC pts who had at least prior 1 line of systemic chemotherapy were enrolled. Median age was 54 years. Baseline ECOG scores were 0 (11 pts) and 1 (20 pts); 29 pts had stage IV disease. There were 19 and 12 pts who had received 1 and ≥2 prior lines of systemic therapy, respectively. The median time from last prior systemic therapy was 16.7 months(m). The efficacy-evaluable population (30 CC pts) had an overall response rate (ORR; best response) of 53.3% (16/30, 3 responders unconfirmed), including 4 CR and 12 PR. The disease control rate was 86.7%. The median time to response was 1.4 months. Median progression free survival (PFS) and 24m PFS rate was 8.4 m and 31.0%, respectively. Median overall survival (OS) was not reach and 24m OS rate was 51.6%. The ORRs of PD-L1 positive, PD-L1 negative, and PD-L1 NA populations were 61.5% (8/13), 55.6% (5/9), and 37.5% (3/8), respectively. One CC pt with negative PD-L1 expression achieved CR and remains on treatment for over 3 years. Thirty pts (96.8%) had ≥ 1 TEAEs; 13 (41.9%) pts had grade ≥ 3 TRAEs. The most common grade ≥ 3 TRAEs included rash (12.9%), lymphocyte count decreased (9.7 %), and decreased platelet count (6.5%). Conclusions: Onatasertib in combination with tori is tolerable with encouraging response rate and disease stabilisation in CC pts at the RP2D combination dose, regardless of PD-L1 expression. Enrolment in the expansion cohort for CPI-treated CC is ongoing, and updated data will be presented. Clinical trial information: NCT04337463 .
Imlunestrant, an oral selective estrogen receptor degrader (SERD), as monotherapy and in combination with abemaciclib, in endometrioid endometrial cancer (EEC): Results from the EMBER phase 1a/1b study.
Authors: Yonemori Kan , Banda Kalyan , Boni Valentina , Sohn Joohyuk , Meniawy Tarek , Lombard Janine Margaret , Kaufman Peter A. , Richardson Debra L. , Bender Somme Laura , Matsumoto Koji , Giridhar Karthik , Garcia Saenz Jose Angel , Prenen Hans , Doger de Spéville Uribe Bernard , Dizon Don S. , García-Corbacho Javier , Li Yujia , Nguyen Bastien , Ismail-Khan Roohi , Neven Patrick 
Published: June 2024

5589 Background: Imlunestrant is a next-generation oral SERD designed to deliver continuous estrogen receptor (ER) target inhibition aimed to improve outcomes for patients (pts) with ER+ cancers. In the first-in-human Phase 1a/1b EMBER trial (NCT04188548), imlunestrant showed favorable safety, pharmacokinetics, and clinical benefit in pre-treated pts with ER+ advanced breast cancer or EEC. Here, we report updated imlunestrant monotherapy data and the first clinical data of imlunestrant + abemaciclib in ER+ EEC pts from EMBER. Methods: Eligible pts had ER+ EEC previously treated with (or deemed inappropriate for) platinum-containing chemotherapy. Prior fulvestrant or aromatase inhibitor therapy was not allowed. In Phase 1a, pts received imlunestrant alone, and in Phase 1b, pts were randomized (1:1) to imlunestrant alone or with abemaciclib. Plasma samples were collected at baseline (all pts) and at cycle 2 (monotherapy pts) for ctDNA analysis (Guardant 360 assay) to correlate with clinical benefit. Primary endpoints were RP2D of imlunestrant monotherapy and in combination. Secondary endpoints included safety, tolerability, and overall response rate (ORR), clinical benefit rate (CBR: complete or partial response, or stable disease ≥24 weeks), and progression-free survival (PFS) using RECIST v1.1. Results: Overall, 72 pts were treated; 39 pts received monotherapy (33 at 400mg [RP2D] and 6 at 800mg po daily) and 33 pts received imlunestrant (29 at 400mg and 4 at 800mg po daily) + abemaciclib (150mg po twice daily). Baseline characteristics, safety, and preliminary efficacy are presented (Table). For monotherapy, the most common TEAEs (all grade/grade 3) were nausea (36%/3%), diarrhea (26%/0), urinary tract infection (26%/3%), and abdominal pain (21%/8%). For imlunestrant + abemaciclib, the most common TEAEs (all grade/grade 3) were diarrhea (88%/3%), nausea (67%/0), fatigue (49%/9%) and anemia (46%/12%). In the monotherapy arm, pts with deeper (≥ 50%) declines in ctDNA variant allele frequency had a higher CBR (4/7 vs 4/17). Conclusions: Imlunestrant, as monotherapy or with abemaciclib, appears safe and tolerable with preliminary evidence of efficacy in pts with metastatic ER+ EEC. Clinical trial information: NCT04188548 . [Table: see text]
Prospective evaluation of the effect of 3 days of post-chemotherapy dexamethasone on patient reported symptoms in gynecologic oncology patients treated with carboplatin and paclitaxel.
Authors: Hart Hayley , Morse Christopher , Krivak Thomas C. , Miller Eirwen Murray , Crafton Sarah , Wield Alyssa , Olawaiye Alexander , Amjad Ali Imran , Graham Emily , Li Tammy , English Heather , Kinzler Donna Marie , Nakayama John 
Published: June 2024

5618 Background: Chemotherapy is associated with many adverse side effects including nausea, myalgia, and emotional stress. Some providers recommend three days of dexamethasone (supplemental dexamethasone) following chemotherapy in an effort to mitigate these toxicities. This study seeks to determine if supplemental dexamethasone affects patient-reported outcomes in patients receiving carboplatin and paclitaxel. Methods: Patients with gynecologic malignancies receiving carboplatin and paclitaxel every 3 weeks were eligible. In this prospective case-control study, patients receiving (cases) supplemental dexamethasone (8mg once daily x 3 days starting on post-chemotherapy day 1) were compared with those patients that did not receive delayed dexamethasone (controls). Decision for supplemental dexamethasone was based on provider’s discretion. The FACT-G7, a validated survey assessing the impact of chemotherapy on patients’ quality of life, was administered by telephone one week after each chemotherapy cycle for up to 6 cycles. Pain during post-chemotherapy days 1-3 was also assessed with an additional survey question. FACT-G7 composite score was our primary outcome of interest. The student’s t-test was used to compare the FACT-G7 and average pain scores between cases and controls at each survey point. Results: Fifty-two patients were enrolled, 26 received supplemental dexamethasone and 26 did not. At interim analysis, 94% of subjects have completed all 6 survey time points. The initial response rate was 98.0%. FACT-G7 scores (Table) were significantly higher, corresponding to less symptoms, in patients treated with supplemental dexamethasone after cycles 4-6. Pain scores in post-chemotherapy days 1-3 were lower following cycle 3 for the supplemental dexamethasone group (p=.0083). Conclusions: Supplemental dexamethasone after carboplatin and paclitaxel for patients with gynecologic malignancies improves patient-reported outcomes. This improvement was limited to cycles 4-6, suggesting possible mitigation of cumulative chemotherapy toxicities.[Table: see text]
The efficacy and safety of presurgical therapy with tislelizumab and axitinib for renal cell carcinoma with inferior vena cava tumor thrombus.
Authors: Wang Xuegang 
Published: June 2024

e16508 Background: There is no currently consensus on presurgical therapy for renal cell carcinoma (RCC) with inferior vena cava (IVC) tumor thrombus. Tyrosine kinase inhibitor (TKI) combined with immune checkpoint inhibitor (ICI) had shown a survival benefit in metastatic RCC patients in clinical trials. However, the efficacy of presurgical therapy with combined ICI and TKI for nonmetastatic RCC with IVC tumor thrombus has not been adequately investigated. Methods: We retrospectively evaluated 7 patients of nonmetastatic RCC with IVC tumor thrombus treated with tislelizumab and axitinib as presurgical therapy and radical nephrectomy and tumor thrombectomy at the First Affiliated Hospital of Xiamen University from May 2020 to December 2022. All patients received combination therapy of tislelizumab and axitinib preoperatively for 3 cycles. The IVC tumor thrombus improvement by Mayo level and diameter were evaluated on magnetic resonance imaging (MRI), and clinical response of primary renal mass and adverse events (AEs) were evaluated using Response Evaluation Criteria in Solid Tumors 1.1 criteria and National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 criteria. Results: 7 RCC with IVC tumor thrombus patients received neoadjuvant tislelizumab combined axitinib, with a median age of 62 (50-72) years. 71.4% (5/7) were male, 71.4% (5/7) were diagnosed histologically with clear cell RCC, while 28.6% (2/7) were Type I papillary RCC. 57.1% (4/7) were Mayo level 2 tumor thrombus and 42.9% (3/7) were Mayo level 3. At follow-up after systematic therapy, 57.1% (4/7) patients had a reduction in Mayo level of tumor thrombus. The median decrease in thrombus dimeter and length was 5.3 (1.8-17.2) mm and 18.5 (4.4-41.5) mm, respectively. The overall response rate (ORR) in primary renal mass was 57.1% (4/7) with 4 partial responses (PR). Radical nephrectomy and thrombectomy were performed for all 7 patients at 1.5 months after finish of presurgical therapy, with 5 patients performed robotic surgery and 2 patients performed open surgery. 3 patients were planned to have hepatic vein clamping and liver mobilization but following treatment, neither of these manoeuvers was needed. The median operative time was 293 (240-322) minutes, the median blood loss was 1187 (750-2000) mL. The most common AE were all grade 1-2, only 1 patient occurred grade 4 liver function injury which did not affect normal operation after symptomatic treatment. During a median follow-up of 24.9 (14.0-45.0) months, only 1 patient had local IVC tumor thrombus metastasis, disease recovered stabilized after stereotactic radiotherapy. Conclusions: Presurgical therapy with tislelizumab and axitinib for RCC patient could be effective in reducing IVC tumor thrombus and were able to undergo easier radical surgery without serious AE.
Real-world data (RWD) with avelumab in patients (pts) with locally advanced or metastatic urothelial cancer (la-mUC): The AVEBLADDER study.
Authors: Sotelo Marta , Pelaez Mireia , Basterretxea Laura , Varga Estrella , Sánchez-Escribano Ricardo , Pujol Eduardo , Santander Carmen , Martinez-Kareaga Mireia , Arruti Ibarbia Mikel , Rodríguez Ledesma Inma , Álvarez-Fernández Carlos , Piedra Pablo , Calderero Veronica , Lainez Nuria , Verdun Aguilar Juan Antonio , Gil-Arnaiz Irene , Fernandez Ricardo , Mazas Cristina , Duran Ignacio 
Published: June 2024

e16559 Background: Current standard of care for la-mUC pts who show no progression after platinum-based chemotherapy is maintenance with avelumab based on survival improvement (JAVELIN 100; Powles et al. NEJM 2020). However, the available RWD evidence on the use of avelumab in the E.U. is limited and there are concerns about the low uptake of this strategy based on figures from American series (Mamtani R et al; JAMA Netw Open 2023). We present here data on the use of avelumab in a large cohort of pts from different centres in Spain within the academic group GO NORTE. Methods: AVEBLADDER is a retrospective observational analysis in which clinical information was retrieved from pts treated across 14 centres in 13 provinces in Northern Spain. The study population included adult pts diagnosed with la/mUC (January 1, 2021-June 30, 2023) followed from date of diagnosis until death, loss to follow-up or end of study. Median overall survival (OS) was determined using the Kaplan-Meier method. Results: 419 pts were included. Median age was 71 [range 42-88]; 80% were males; 81% had primary bladder tumours and 94% predominant urothelial histology. Seventy three percent of pts had visceral/bony metastases and 59% were unfit for cisplatin. Most common 1st line treatment (tx) [88%] was platinum-based chemotherapy [median number of cycles 4]. Out of 369 pts who received platinum-based chemotherapy, non-progression (CR, PR or SD) was reported in 230 pts [62%], of whom only 85 pts [37%] received maintenance avelumab. Fifty-eight pts treated with avelumab were evaluable for response: 7 (10 %) achieved a CR, 12 (14%) PR, 22 (26%) SD and 17 (20%) PD. The most common reason for non-receiving avelumab in our series was lack of access/reimbursement according to country/region policy. Overall, 168 pts [40%] started 2nd line tx and atezolizumab was the most used agent, only 41 pts [24%] received third line tx. With a median follow-up of 11 months, 194 pts [46%] are still alive and median overall survival (OS) is estimated to be 28 months (95% CI 23-not reached) with maintenance avelumab vs 11 months (95% CI 9-13) for those who did not receive this drug. Conclusions: Despite the demonstrated improvement in OS for maintenance avelumab, its uptake in our series was low with roughly 40% of the pts. New policies and better access to the drug will most likely improve these figures and hopefully also the proportion of patients who progress to receive a third line where novel therapies are currently being implemented. AVEBLADDER is a study sponsored by GO NORTE a non-for-profit GU cooperative group.