bluuebunny/crossref_metadata_2025_split huggingface dataset:
Is there a role for conventional-dose chemotherapy in relapsed germ cell tumors?
Authors: Manhaes Luana Toledo , Gomes Daniel Musse , Small Isabele , Araujo Luiz H. , Domingues Pedro Masson 
Published: February 2020

404 Background: Patients with germ cell tumors (GCT) that relapse after first-line platinum-based chemotherapy can still be successfully rescued with second-line regimens. High-dose chemotherapy has shown favorable outcomes, and is a preferred option in most instances. Herein, we argued if conventional-dose chemotherapy (CDCT) could also be an alternative in selected patients. Methods: We performed a retrospective observational study, analyzing medical data of 57 GCT male patients treated with salvage chemotherapy after relapse to first-line platinum-based treatment from 2000 to 2015 at the Brazilian National Cancer Institute. Results: The median age was 28 years (range 15 to 49). 26 patients (46%) were Afro-Brazilian, 45 (79%) were non-seminoma, and 53 (93%) had primary testis tumors. 14 patients (25%) had bone, liver or brain metastasis at relapse, and in 35 (61%) the progression-free interval (PFI) after first-line was < 3months. The International Prognostic Factors Study Group (IPFSG) risk classification at relapse for very-low/low, intermediate and high/very-high risk were 8 (14%), 25 (44%), 24 (42%), respectively. After a median follow-up of 8 years, the 2-year PFS was 30% (95% IC, 20 % to 45 %) and the 2-year overall survival (OS) was 34% (95% IC, 23% to 49%). PFI < 3m after first-line (HR 2,38; p<0,005) and AFP > 1000 at relapse (HR 2,38, p<0,023) were negative prognostic factors for PFS and OS. The 2-year PFS and OS for IPFSG risk classification very-low/low, intermediate and high/very-high risk were 75% and 73%, 28% and 32%, 18% and 24%, respectively. Conclusions: In patients with relapsed GCT and very-low/low risk disease by the IPFSG classification, CDCT may be a reasonable option, achieving long-term survival rates. However, CDCT was associated with poor outcome in intermediate and high/very-high risk groups. Further studies should be conducted to assess the best treatment in this subset, since even in second-line, many of patients are still potentially curable.
Overall survival (OS) among Medicare beneficiaries receiving sipuleucel-T (sip-T) versus oral treatment for metastatic castration-resistant prostate cancer (mCRPC).
Authors: McKay Rana R. , Flanders Scott C. , Ferro Christine , Fitch Kate , Fabrizio Michael , Schweizer Michael Thomas 
Published: February 2020

42 Background: Since the mCRPC treatment landscape is evolving, we examined real-world use and outcomes of sipuleucel-T (sip-T) and oral agents (abiraterone acetate and enzalutamide) in men with mCRPC. Methods: Using Medicare FFS Identifiable Research data, we identified mCRPC men with a qualifying prostate cancer diagnosis (ICD-9 185, ICD-10 C-61) and an initial treatment claim (abiraterone, cabazitaxel, docetaxel, enzalutamide, radium 223, sip-T) in 2014. Continuous Part A, B, and D eligibility and no HMO enrollment was required through 2017 or until death. mCRPC index date is the date of a mCRPC therapeutic claim. Using 4 groups (sip-T first line, oral first line, sip-T any line, and oral any line [no sip-T]), survival was estimated using Kaplan-Meier methods (unadjusted). Hazard ratios (HR) were estimated using Cox’s proportional hazards regression modeling. Results: During 2014, 14,482 eligible men had mCRPC drug claims. We studied 6,853 naïve mCRPC men with no treatment claim in the prior 12 months. Over 150 permutations of anti-cancer agents were identified. See table for patient characteristics. Sip-T was used 2+ line in 4.5% of men receiving orals 1st. Median overall survival was longer for men who received sip-T, regardless if used 1st line (35 mo) or in any line (35 mo), compared with oral 1st line use (21 mo) or an oral any time without sip-T (21 mo). Similar survival was seen after adjusting for baseline opioid use. While most received sip-T as 1st line, survival rates were higher in men receiving sip-T in any line (48%) compared to men who never received any sip-T (29%). Conclusions: In this analysis, sip-T use was associated with a 45% reduction in risk of death and 14 mo survival benefit in the Medicare FFS population regardless of when used. Real-world analyses like this provide insight into how to optimize sip-T use to treat prostate cancer.[Table: see text]
Study EV-103: Preliminary durability results of enfortumab vedotin plus pembrolizumab for locally advanced or metastatic urothelial carcinoma.
Authors: Rosenberg Jonathan E. , Flaig Thomas W. , Friedlander Terence W. , Milowsky Matthew I. , Srinivas Sandy , Petrylak Daniel Peter , Merchan Jaime R. , Bilen Mehmet Asim , Carret Anne-Sophie , Yuan Nancy , Sasse Carolyn , Hoimes Christopher J. 
Published: February 2020

441 Background: Platinum chemotherapy is the standard for patients (pts) with metastatic urothelial carcinoma (mUC) in the first line (1L) setting. In cisplatin-ineligible pts, gem/carbo is a standard therapy, but is poorly tolerated with limited durability and survival. PD-1/PD-L1 inhibitors, such as pembrolizumab (P), have shown promising durability in this setting for PD-L1 high patients. Enfortumab vedotin (EV) is an antibody-drug conjugate that delivers the microtubule-disrupting agent MMAE to cells expressing Nectin-4, which is highly expressed in UC. EV has shown activity in previously treated mUC. Initial EV + P data were previously presented (Hoimes ESMO 2019); this provides first durability data and an update on safety/ORR. Methods: This multicohort study (NCT03288545) evaluated the safety/activity of EV + P. We report a cohort of 1L cis-ineligible patients treated with EV 1.25 mg/kg + P. In each 3-week cycle, EV was administered on Days 1 and 8 and P on Day 1. The primary endpoint was safety/tolerability; secondary objectives included determination of recommended EV dose, ORR, DCR, DOR/PFS per RECIST v1.1, and OS. Results: As of 8 Oct 2019, 45 mUC pts (median age 69 yr [51–90]) received a median of 9 (range 1-22) cycles of EV + P. The most common treatment-emergent adverse events (AE) were fatigue (58%, 11% ≥G3), alopecia (53%), and peripheral sensory neuropathy (53%, 4% ≥G3). One pt died due to an AE reported as related (multiple organ failure). With a median follow-up of 11.5 mo, confirmed investigator-assessed ORR was 73.3% (95% CI, 58.1, 85.4) including 15.6% CRs; DCR was 93.3%. The ORR in pts with liver metastasis was 53.3% (8/15). The ORR in pts with available PD-L1 status was 78.6% in PD-L1 high (11/14) and 63.2% in PD-L1 low (12/19). Of the 33 responders, 18 (55%) have ongoing responses including 11 responses beyond 10 months. The median DOR was not reached (range 1.2 to 12.9+ mo). The median PFS was 12.3 mo (95% CI, 7.98, -). Conclusions: In 1L cis-ineligible pts with mUC, EV + P, a potential platinum free option, demonstrates promising activity and durability, with a manageable safety profile. Further evaluation of EV + P in mUC and muscle-invasive UC is ongoing. Clinical trial information: NCT03288545.
PET imaging urothelial bladder cancer: A novel approach.
Authors: Thakur Mathew L. , Gomella Leonard G. , Tripathi Sushil K. , Salmanoglu Ebru , Keith Scott W. , Kelly William Kevin , Hoffman-Censits Jean H. , Kim Sung , Intenzo Charles M. , McCue Peter , Trabulsi Edouard John 
Published: February 2020

443 Background: Urothelial bladder cancer (UBC) inflicts >80,000 new patients annually. Since treatment is stage-dependent, accurate staging is crucial. Conventional imaging and biopsy are often unreliable. A large number of PET tracers, developed to improve imaging, have limitations e.g. urinary excretion compromising their ability to assess the bladder lumen and invasive tumors. This study is to validate a hypothesis that high density VPAC receptors expression on UBC cell surface, can be targeted to PET image UBC, to determine loco-regional disease and metastatic lesions. Methods: Cu-64-TP3805 (4±10% mCi), with its high affinity (3.1 x 10−9M) for VPAC, was given IV to 19 UBC patients (44-80 yrs), scheduled for radical cystectomy. Those eligible for neoadjuvant chemotherapy were treated as such. Urine and blood samples were collected on the day of scan. Whole body PET/CT images acquired 60 to 90 min later and read by two physicians. Surgery was performed 1 to 4 weeks later. Imaging results were correlated with histology. Results: There were no adverse events. Urinary excretion of Cu-64-TP3805 was negligible. Blood clearance was biphasic (t ½ a = 22.3 ±2.7 min ~ 85% and t ½ β = 118.2 ± 4.9 min ~ 15%). VPAC PET bladder images were true positive (TP) in 11, true negative (TN) in 4, false positive (FP) in 1 and false negative (FN) in 3 patients with 79% sensitivity (95% CI 49%-95%), 80% specificity (95% CI 28%-100%), 92% PPV (95% CI 62%-100%), and 57% NPV (95% CI 18%-90%). Prostate images were TP in 8, TN in 6, and FP in 5 patients, with 100% sensitivity (95% CI 63%-100%), 55% specificity (95% CI 23%-83%), 62% PPV (95% CI 32%-86%), and 100% NPV (95% CI 54%-100%). The 5 FP images revealed HGPIN on re-analysis. For lymph nodes, images were TP in 1, TN in 14 and FN in 4 patients, with 25% sensitivity (95% CI 1%-81%), 100% specificity (95% CI 78%-100%), 100% PPV (95% CI 3%-100%), and 83% NPV (95% CI 59%-96%). In one patient, several lesions were seen in the spine and iliac crest. Biopsy was positive for metastasis. In smokers (N=12) there was diffused or focal tracer uptake in the lungs. In 7 non-smokers, 3 with CT depicted abnormality had tracer lung uptake and 4 did not. Conclusions: These first in human pilot study data depict Cu-64-TP3805 VPAC targeting to image UBC as worthy of further investigation.
Replacing TURBT with mpMRI for staging MIBC: Pilot data from the BladderPath study.
Authors: James Nicholas D. , Pirrie Sarah , Liu Wenyu , Amir Rashid , Gallagher Jean , Hughes Ana , Jefferson Kieran , Knight Allen , Nanton Veronica , Mintz Harriet Paige , Pope Ann , Catto James WF , Patel Prashant , Bryan Richard T. 
Published: February 2020

446 Background: The diagnostic pathways for bladder cancer are largely unchanged for 30 years. The BladderPath trial objectives are to: improve staging, accelerate treatment, and reduce iatrogenic tumour spread by avoiding TURBT. We hypothesise that substituting TURBT with mpMRI will avoid unnecessary surgery, accelerate correct MIBC treatment and improve outcomes. Methods: A randomised phase 2/3 trial of standard of care (Pathway 1) versus risk-stratified mpMRI-directed care (Pathway 2) in visually-diagnosed incident bladder cancer. Patients with bladder lesions suspicious for malignancy at flexible cystoscopy are stratified by a 5-point Likert scale: strongly agree (1) or agree (2) that the lesion is NMIBC, equivocal (3) NMIBC or MIBC, and agree (4) or strongly agree (5) the lesion is MIBC. All patients are randomised; those with probable NMIBC (Likert 1 & 2) undergo TURBT in both pathways, and those with possible MIBC (Likert 3-5) undergo TURBT (Pathway 1) or mpMRI (Pathway 2). Endpoints: feasibility, time to correct MIBC therapy and clinical progression-free survival. We report preliminary feasibility data. Results: To date, 218 potentially eligible patients have been registered; on cystoscopy, 151 patients had no bladder lesions and 5 were excluded for other reasons. Of 62 patients randomised, we report results from 45 with preliminary data. Of the 21 patients in Pathway 1, 11 patients classified as probable NMIBC underwent TURBT (pathology: 11/11 NMIBC); 9/10 patients classified as possible MIBC underwent TURBT (pathology: 4/9 NMIBC & 5/9 MIBC) and 1 patient incorrectly underwent mpMRI (staging: MIBC). Of the 24 patients in Pathway 2, 11/12 patients classified as probable NMIBC underwent TURBT (pathology: 9/11 NMIBC & 2/11 MIBC) and one patient incorrectly underwent mpMRI (staging: NMIBC); 12 patients classified as possible MIBC underwent mpMRI (staging: 6/12 NMIBC & 6/12 MIBC). Conclusions: A 5-point Likert scale accurately identifies patients with a low risk of MIBC (Likert 1 & 2). It is feasible to randomise possible MIBC patients to TURBT or mpMRI for staging. The study is ongoing to investigate the intermediate outcome of time to correct therapy for MIBC and NMIBC and the final outcome of clinical progression-free survival. Clinical trial information: 35296862.
Oncofid-P-B for the treatment of BCG unresponsive carcinoma in situ (CIS) of bladder: Results of European multicenter phase I study at the end of 12- consecutive weeks intensive course.
Authors: Hurle Rodolfo , Guazzoni Giorgio Ferruccio , Colombo Piergiuseppe , Santoro Armando , De Cobelli Ottavio , Di Trapani Ettore , Nohales Gloria , Carlos Llorente , Duran-Merino Ramon , Lazzeri Massimo 
Published: February 2020

486 Background: There is an unmet clinical need for new drugs able to delay or avoid cystectomy in patients with CIS unresponsive to BCG. Here, we report the safety and efficacy of Oncofid−P-B, is a new drug that originates from the chemical conjugation of paclitaxel with hyaluronic acid, in patients with CIS unresponsive or intolerant to BCG. Methods: This is an open-label, single arm, multicenter international study (Registered as EudraCT Number: 2016-004144-11) to assess safety, tolerability and efficacy of Oncofid-P-B administered in 20 patients with CIS, unresponsive or intolerant to BCG and unwilling or unfit for cystectomy. Oncofid-P-B was administered by intravesical instillation for 12 consecutive weeks (intensive phase). A 12 monthly (maintenance phase) in patients who were in complete response (CR) after the intensive phase is ongoing. The primary end-point was the overall safety profile. Secondary endpoints included i) efficacy after the intensive phase ii) compliance, iii) systemic absorption. The CR is defined as a negative cystoscopy including biopsy of the urothelium and negative cytology. Statistics will be calculated, as appropriate, for the quantitative variables. Results: Of the 20 enrolled patients who completed the intensive phase, CR was achieved in 15 patients (75%). Seven G1-G2 drug-related adverse events (AEs) were reported in only three patients over 240 instillations. No drug related serious AEs and no study withdrawal have been reported. In all plasma samples, the drug concentration was always below the Limit of Quantification (0.1ng/ml). Over 15 patients who ended the intensive course without CIS recurrence, five already completed the 12-month maintenance phase (four patients with no recurrence of CIS), thirteen were disease free after three months and six are completing the maintenance. Conclusions: The excellent safety profile of Oncofid-P-B is well positioned as compared with the most recent competitors, thus confirming its potential as therapeutic option in BCG unresponsive CIS patients, also with a prolonged treatment schedule, and deserves further clinical evaluation. Clinical trial information: 2016-004144-11.
A phase I/II feasibility study of cetuximab with 5FU and mitomycin C or cisplatin with concurrent radiotherapy in muscle invasive bladder cancer.
Authors: James Nicholas D. , Pirrie Sarah , Liu Wenyu , Ford Daniel , Zarkar Anjali , Southgate Elizabeth , Desai Amisha , Hussain Syed A. 
Published: February 2020

491 Background: Chemoradiotherapy (cRT) with 5FU and Mitomycin C (5FU/MMC) is an accepted standard of care for muscle invasive bladder cancer. Cetuximab is an approved radio-sensitiser in head and neck cancer and EGFR is over-expressed in bladder cancer. We report a phase 1/2 trial of the addition of cetuximab to standard cRT. Methods: Phase 1/2 single-arm, multicentre, open-label study conducted in 5 UK centres. Treatment: RT: 64 Gy/32 fractions, 5FU 2.5g/m2 over days 1-5 & 22-26, MMC 12g/m2 day 1, cetuximab 400mg/m2 day -8, 200mg/m2 day 1 and weekly x7. Main inclusion criteria: T2-4aN0M0 urothelial cancer, PS 0-1; prior neoadjuvant therapy permitted. Endpoints: Phase 1; feasibility and safety of cRT with cetuximab + 5FU/MMC in combination. Phase 2; local control (LC) at 3 months. Secondary outcomes: invasive loco-regional progression free survival (LPFS), noninvasive LPFS, metastasis free survival (MFS), overall survival (OS) & patient reported outcomes (PROMs). Sample size; phase 1 between 6 and 18, phase 2 up to 45 including those recruited in phase 1. Results: Between Sept 2012 and Oct 2016, 33 patients were recruited; 7 in phase 1 26 in phase 2. Median age 70.1 (IQR 65.4-80.2) yrs, 60.6% WHO Performance Status 0; 81.8% male, 26/33 neoAd chemotherapy. 3 patients ineligible post registration. 30 evaluable pts started RT, 1 patient didn’t complete RT due to serious adverse event (interstitial pneumonitis), 3 with delays. Phase 1, 6/7 pts completed Cetux therapy, 1 omitted 1 dose for grade 3 rash. LC was 77% (95% CI 58, 90). Overall median dose intensities Cetux 100%, MMC 99% 5FU 99.8%. 8 pts developed recurrence; 2 MIBC. The 6 & 12 month muscle-invasive LPFS was 93 &; non-invasive LPFS 97% & 85%, MFS 90% & 90%, OS 97% & 87%. PROMs showed a transient dip at 1 mo, back to baseline at 3 mo. Conclusions: Phase 1 data demonstrate it’s feasible and safe to add cetuximab to cRT with 5FU/MMC with high delivered dose intensities. Although recruitment failed to reach the pre-specified target for phase 2 exploratory analysis indicate the 3 month bladder control rates and recurrence rates are above those reported in BC2001 with good PROMs provides evidence to consider further evaluation of cetuximab. Clinical trial information: 80733590.
Effect of concurrent proton pump inhibitors (PPI) use in patients (pts) treated with immune checkpoint inhibitors (ICI) for metastatic urothelial carcinoma (mUC).
Authors: Morales-Barrera Rafael , Vidal Casinello Natalia , Bonfill Teresa , Domenech Montserrat , Suarez Rodriguez Cristina , Puente Javier , Joaquin Julia Giner , Figols Mariona , Galante Isabel , Carrion Albert , Lopez Hector , Gonzalez Macarena , Roche Sarai , Mateo Joaquin , Gallardo Diaz Enrique , Fernández Sáez Carlos , Valverde Morales Claudia Maria , de Torres Ines , Morote Juan , Carles Joan 
Published: February 2020

500 Background: PPI are widely used in pts with cancer. PPI are associated with anti-inflammatory properties and direct effects on neutrophils and monocytes that might prevent inflammation. We investigate the role of PPI on outcomes of pt receiving ICI in mUC. Methods: Medical records from pts with mUC treated with ICI from May 2013 to May 2019 using a multi-institutional database was evaluated. Use of PPI was defined: 30 days prior, during the treatment and 30 days after the last dose of ICI. ORR were assessed according to RECIST v1.1. The X2 test was used to determine differences in rates. PFS and OS were estimated using Kaplan-Method and long rank test was used to assess differences between groups. All analyses were performed using SPSS v21. Results: Overall, 115 pts received therapy with ICI. Of these pts, 20 were not included due to the absence of information about PPI. Thus, 95 pts were included for the analysis. 50 (52.6%) pts received PPI. Median age was 68 years, 79 pts (83.2%) were male, 78 pts (82.1%) had ECOG PS 0-1, 20 pts (21.1%) had liver metastasis and 36 pts (37.9%) received ICI treatment as frontline therapy. ICI prescribed were atezolizumab (58.9%), pembrolizumab (17.9%), durvalumab (12.6%), nivolumab (6.3%) and durvalumab/tremelimumab (4.2%). Pts with no PPIs use had higher ORR (CR [8.9%] +PR [14.4%]) compared to those pt who use PPIs (CR [4.4%] + PR [8.9%]) (P=0.197). Median PFS was 10.05 mo (95% CI: 3.86-16.27) for non PPI users and 3.87 mo (95% CI:1.84-5.91) for PPI users (P=0.04). Median OS was 19.71 mo (95% IC:8.93-30.49) for non PPI users and 7.9 mo (4.4-11.45) for PPI users (P=0.072). Conclusions: We have observed shorter PFS and trend toward lower OS and ORR for PPI users. The real impact of PPI should be confirmed in prospective studies.
Does escalation results from phase Ib/II Norse study of erdafitinib (ERDA) + PD-1 inhibitor JNJ-63723283 (Cetrelimab [CET]) in patients (pts) with metastatic or locally advanced urothelial carcinoma (mUC) and selected fibroblast growth factor receptor (FGFR) gene alterations.
Authors: Moreno Victor , Loriot Yohann , Valderrama Begona Pérez , Beato Carmen , Vano Yann-Alexandre , Fleming Mark T. , Duran Ignacio , Siena Salvatore , Tolbert Jaszianne A. , OHagan Anne , Akapame Sydney , Lau Yvonne Y. , Geoffrois Lionnel , Tagawa Scott T. , Mellado Begona , Siefker-Radtke Arlene O. 
Published: February 2020

511 Background: ERDA, an oral pan-FGFR inhibitor, is approved by the US FDA for pts with metastatic urothelial carcinoma (mUC) with susceptible FGFR3/2 gene alterations and progressed after ≥1 line of prior platinum-containing chemotherapy (PCC).1 CET, an IgG4, binds to anti-programmed cell death proteins (PD-1) and has shown activity in solid tumors.2 ERDA+CET may demonstrate complementary mechanisms as neoantigen release by ERDA may prime the tumor microenvironment for response. NORSE is a phase 1b/2 study to evaluate ERDA+CET in pts with mUC. Methods: Adult mUC pts with specific FGFR alterations who have progressed after ≥1 prior systemic therapy and no prior FGFR or PD-1/PD(L)-1 inhibitors enrolled in 3 dose levels (DL) of ERDA (DL1: 6 mg, DL2A: 8 mg, DL2: 8 mg with uptitration [UPT] to 9 mg) + CET (IV, 240 mg). Cohorts enrolled until dose limiting toxicity (DLT) or RP2D was identified. Primary endpoints: DLT and adverse events (AEs). Results: Of 15 pts (DL1: 4, DL2A: 3, DL2: 8), 11 continued on treatment at the time of the data cut. 14/15 pts experienced AEs; 3 experienced serious unrelated AEs (urinary tract infection, urosepsis, and large intestinal obstruction) all in DL1, 2 led to death; 10 experienced Grade >3 AEs and 2 experienced AEs of special interest, considered related to ERDA (Table). No DLTs were observed in any cohorts, 8 mg with UPT + CET was established as the RP2D. At data cut-off, investigator-assessed best overall response rate (CR+PR+uCR+uPR) in pts treated with the RP2D was 71% and disease control rate was 100% for RECIST 1.1 evaluable pts (n=7). Conclusions: 8 mg ERDA with UPT+240 mg CET was well tolerated and established as the RP2D. The combination of ERDA+CET is being further explored in the ongoing randomized phase 2 study in first-line cisplatin-ineligible mUC pts (NCT03473743). Clinical trial information: 2017-001980-19. [Table: see text]