bluuebunny/crossref_metadata_2025_split huggingface dataset:
An in-depth multicentered population-based analysis of outcomes of patients with metastatic renal cell carcinoma (mRCC) that do not meet eligibility criteria for clinical trials.
Authors: Heng Daniel Yick Chin , Choueiri Toni K. , Lee Jae-Lyun , Harshman Lauren Christine , Bjarnason Georg A. , Knox Jennifer J. , MacKenzie Mary J. , Vaishampayan Ulka N. , Yuasa Takeshi , Tan Min-Han , Rha Sun Young , Donskov Frede , Agarwal Neeraj , Pal Sumanta Kumar , Kollmannsberger Christian K. , North Scott A. , Rini Brian I. , Wood Lori 
Published: March 2020

4536 Background: Clinical trials have strict eligibility criteria that exclude many patients to whom the trial results are later extrapolated to in clinical practice. Methods: mRCC patients treated with VEGF targeted therapy were retrospectively deemed ineligible for clinical trials (according to commonly used inclusion/exclusion criteria) if they had a Karnofsky Performance Status (KPS) <70%, brain metastases, non-clear cell histology, hemoglobin<=9 g/dL, creatinine >2x the upper limit of normal, platelet count of <100x103/uL, neutrophil count <1500/mm3 or corrected calcium>=12 mg/dL. Results: 894/2076 (43%) patients were deemed ineligible for clinical trials by the above criteria. Between ineligible versus eligible patients, the response rate, median progression free survival (PFS) and median overall survival of first-line targeted therapy were 21% vs 29%, 5.2 vs 8.8 months and 14.5 vs 28.8 months (all p<0.0001), respectively. Second-line PFS (if applicable) was 3.2 months in the trial ineligible vs 4.4 months in the trial eligible patients (p=0.0074). Patients who were excluded due to KPS<70, hemoglobin<=9 g/dL, calcium >=12, brain metastases, and non-clear cell histology, had a hazard ratio (HR) for death of 2.8 (95%CI 2.4-3.4), 1.8 (95%CI 1.4-2.2), 1.8 (95%CI 1.2-2.7), 1.4 (95%CI 1.1-1.8), and 1.4 (95%CI 1.1-1.7), respectively (all p<0.01). When adjusted by the Heng et al prognostic categories, the HR for death between trial ineligible vs trial eligible patients was 1.511 (95%CI=1.335-1.710, p<0.0001). Conclusions: The number of patients that are ineligible for clinical trials is high and their outcomes are inferior. Specific trials addressing the needs of protocol ineligible patients and assessing OS are required. [Table: see text]
Phase III randomized sequential open-label study to evaluate efficacy and safety of sorafenib (SO) followed by sunitinib (SU) versus sunitinib followed by sorafenib in patients with advanced/metastatic renal cell carcinoma without prior systemic therapy (SWITCH Study): Safety interim analysis results.
Authors: Michel Maurice Stephan , Vervenne Walter , Goebell Peter J. , Von Weikersthal Ludwig Fischer , Freier Werner , De Santis Maria , Zimmermann Uwe , Bos Monique M.E.M. , Trojan Lutz , Lerchenmuller Christian A. , Schenk Marcus , Staehler Michael D. , Flörcken Anne , Pahernik Sascha , Los Maartje , Van Arkel Cornelis , Schirrmacher-Memmel Silke , Eichelberg Christian 
Published: March 2020

4539 Background: Several retrospective studies have investigated the sequential use of SO and SU. Some smaller trials support the use of SO followed by SU forming the rationale for this study. Methods: Pts with metastatic RCC unsuitable for cytokines without prior systemic therapy, ECOG PS 0/1, MSKCC score low or intermediate, and ≥1 measurable lesion (CT/MRI every 12 weeks) were randomized to SO->SU or SU->SO in standard dosage (primary endpoint total PFS from randomization to event during 2nd line therapy). Treatment continues until progression or intolerability. Monitoring includes echocardiography and NT pro-BNP. Results: Baseline characteristics of 361 randomized pts (116 completed) are balanced between arms. Safety data of 333 pts are evaluable. AE occurring in >10% of pts are listed in tab. 1. Left-ventricular ejection fraction (LVEF) at screening, switch of treatment, and end of study are given in tab. 1. AE occurred in 93.4% and 92.8%; grade 3/4 AE in 59.9% and 50%; and SAE in 46.7% and 42.2% in the SO->SU and SU->SO arm, respectively. Updated results will be presented. Conclusions: AE frequencies are higher in 1st than in 2nd line treatments. Typical AE profiles for SO and SU are observed. LVEF values are in a similar range. [Table: see text]
The use of tumor growth rate (TGR) in evaluating sorafenib and everolimus treatment in mRCC patients: An integrated analysis of the TARGET and RECORD phase III trials data.
Authors: Ferte Charles , Albiges Laurence , Soria Jean-Charles , Loriot Yohann , Fizazi Karim , Escudier Bernard J. 
Published: March 2020

4540 Background: RECIST criteria may not be sufficient to evaluate targeted therapies in mRCC. TGR includes the time between each evaluation and is expected to overcome some of the RECIST pitfalls. How TGR is modified under targeted therapies and how it correlates with outcome in mRCC remains unknown. Methods: Medical records from all patients (pts) prospectively treated at Institut Gustave Roussy (IGR) in the TARGET (n=84) and in the RECORD (n= 52) phase III trials were extracted. Results were subsequently validated in the entire TARGET cohort (TARGET) (n=902). TGR was computed by dividing tumor shrinkage by the time between the two related evaluations (% RECIST x 100 / days). Typical treatment periods were assessed: BEFORE treatment (wash-out), UNDER treatment (first cycle), at PROGRESSION (pts still receiving the drug) and AFTER treatment interruption (wash-out). Results: As compared to placebo, TGR UNDER was significantly decreased following sorafenib (-23.6 vs. 20 (IGR) and -19 vs. 22 (TARGET)) and everolimus (-5.2 vs. 30 (IGR)). The great majority of pts (IGR) had a decrease in the TGR UNDER vs. BEFORE, regardless of the RECIST evaluation, both with sorafenib (28/29) or everolimus (36/37). TGR AFTER sorafenib or everolimus interruption was significantly higher than TGR at PROGRESSION in both settings (IGR) (14.6 vs. 31 and 17.9 vs. 32.1 respectively). No significant difference was observed between TGR AFTER vs. BEFORE either in sorafenib or in everolimus pts (IGR). High TGR UNDER is associated with poor progression free survival (HR= 2.6) and overall survival (HR= 2.3) in sorafenib-treated pts (multivariate analysis, trained in IGR and validated in TARGET cohorts) and with poor overall survival in everolimus-treated pts (IGR)(HR= 1.2). Conclusions: Adding TGR assessment in mRCC unravels interesting traits that make it potentially adaptable for clinical practice: (i) better evaluation of the tumor response, regardless of RECIST criteria, (ii) independent prognosis value, (iii) it suggests that maintaining sorafenib or everolimus after disease progression might benefit to patients and should be prospectively evaluated.
Phase II trial of RAD001 in renal cell carcinoma patients with non-clear cell histology.
Authors: Koh Youngil , Kim Ji Yeon , Lim Ho Yeong , Ahn Jin-Hee , Lee Jae-Lyun , Rha Sun Young , Kim YuJung , Kim Tae Min , Lee Se-Hoon 
Published: March 2020

4544^ Background: In non-clear cell renal cell carcinoma (ncRCC), the efficacy of VEGF tyrosine kinase inhibitor (TKI) is controversial. In the while, a mTOR inhibitor, temsirolimus showed a promising efficacy in ncRCC patients in ARCC trial. Hence, we investigated the role of everolimus in ncRCC with this phase II trial. Methods: ncRCC patients received everolimus 10 mg once daily until disease progression or unacceptable toxicity. We included patients who had received VEGF TKI previously, while excluded patients who received previous mTOR inhibitor. The primary end point was progression free survival (PFS). Results: A total of 49 patients were enrolled from 5 centers. Their median age was 57 years (range 24-75 years) and male to female ratio was 37:12. Histology of the patients included papillary (n=29), chromophobe (n=8), collecting duct (n=2), sarcomatoid (n=4), and unclassifiable (n=6) RCC. Twenty-three patients had been treated with VEGF-TKI prior to the study enrollment. Among 49 patients, 46 patients underwent radiologic response assessment after everolimus treatment. Partial response was observed in 5 patients (10.2%) and stable disease in 25 patients (51.0%). Diseases of 16 patients (32.7%) progressed despite of everolimus administration. Histology of 5 patients who showed objective response to everolimus included chromophobe carcinoma (n=2), papillary carcinoma (n=2) and unclassifiable carcinoma (n=1). During the study period, 34 patients experienced PFS events and median PFS was 5.2 months. Patients with chromophobe histology showed longer PFS than patients with the other histologies (median PFS 18.8 months vs. 3.5 months, p=0.027). Estimated median PFS were not significantly different between patients VEGF-TKI treatment and patients without previous VEGF-TKI treatment (median PFS 7.1 vs. 3.7 months, p=0.110). Toxicity profiles were commensurable with previous reports. Conclusions: Everolimus shows considerable efficacy in ncRCC. Patients with chromophobe histology might earn benefit from everolimus treatment especially. Previous treatment with VEGF-TKI seems not to significantly influence outcome of everolimus therapy in these patients. (ClinicalTrials.gov number, NCT00830895)
Phase I trial of ASG-5ME in metastatic castration-resistant prostate cancer (CRPC).
Authors: Morris Michael J. , Bruce Justine Yang , Reyno Leonard M. , Anand Banmeet , Hartford Alan , Jelaca-Maxwell Kathy , Lackey Jacqueline , Eisenberger Mario A. 
Published: March 2020

4568 Background: SLC44A4 is a 710 amino acid protein that is expressed on prostate, pancreas and other cancers. SLC44A4 is found in 95% of primary prostate tumors (75% express moderate to high levels). ASG-5ME is an antibody drug conjugate (ADC) comprised of a fully human antibody targeting SLC44A4, conjugated to the microtubule-disrupting agent monomethyl auristatin E. ASG-5ME has dose-dependent cytotoxic effects in vitro and significant anti-tumor activity in xenograft models. We report results of a phase I study to establish the maximum tolerated dose (MTD) of ASG-5ME for CRPC, conducted by the Prostate Cancer Clinical Trials Consortium. Methods: Patients (pts) had progressive metastatic CRPC. Prior chemotherapy was allowed. Treatment cohorts were 0.3, 0.6, 1.2, 1.8, 2.4, and 3.0 mg/kg. ASG-5ME was given IV q3 weeks. Safety, pharmacokinetic properties, anti-tumor effects, circulating tumor cell (CTC) enumeration, and CTC molecular profiles were assessed. Pts were treated until disease progression or unacceptable toxicity. Dose limiting toxicity (DLT) was defined by cycle 1 toxicity. Results: 20 pts have been treated (3, 3, 3, 3, 6, and 2 pts per respective cohort). Mean age was 69 (range 56-87), median Gleason score 8 (6-10), mean baseline PSA 225 (5-1987). Pts received an average of 4 doses (1-12). 2 DLTs occurred in Cycle 1 in the 3 mg/kg cohort: DLT 1: Grade (Gr) 3 troponin elevation and DLT 2: Gr3 maculopapular rash, hypoxia, constipation, and Gr4 neutropenia. Common Gr 1 and 2 adverse events included fatigue, anorexia, peripheral neuropathy, dyspnea and nausea. Gr3 events included: fatigue (2 pts),peripheral neuropathy (1), dyspnea (1) and nausea (1). Serum concentrations of ASG-5ME decreased multi-exponentially and the exposure was dose-proportional. The half-life of intact drug was calculated as 7.01 days (range-3.93-15.9, n=17) after the first dose and 11.2 days ( range-7.75-19.1 days, n=10) after the last dose. PSA declines of >50% were seen in 3/8 pts treated in the last two cohorts and one unconfirmed >50% decrease in retroperitoneal nodes. Conclusions: DLT events observed at 3 mg/kg exceeded the MTD; the MTD is 2.4 mg/kg of doses tested in pts with metastatic CRPC. The drug appears to have anti-cancer activity at 2.4 and 3 mg/kg.
Intravesical sequential BCG and electromotive mitomycin versus BCG alone in high risk non-muscle invasive bladder cancer.
Authors: Di Stasi Savino Mauro , Verri Cristian , Liberati Emanuele , Zampa Germano , Masedu Francesco , Valenti Marco 
Published: March 2020

4572 Background: In 2006, we reported that intravesical sequential bacillus Calmette-Guérin (BCG) and electromotive mitomycin in high risk non-muscle invasive bladder cancer leads to higher disease-free interval, lower recurrence and progression, and to improved overall survival and disease-specific survival compared with BCG alone. After an additional 6 years of follow-up, we now report estimated 16-year results. Methods: From 1994 through 2002, we randomly assigned 212 patients with high risk non.muscle invasive bladder cancer to 81 mg BCG infused over 120 min once a week for 6 weeks (n=105) or to 81 mg BCG infused over 120 min once a week for 2 weeks, followed by 40 mg electromotive mitomycin (intravesical electric current 20 mA for 30 min) once a week as one cycle for three cycles (n=107). Complete responders underwent maintenance treatment: those assigned BCG alone had one infusion of 81 mg BCG once a month for 10 months, and those assigned BCG and mitomycin had 40 mg electromotive mitomycin once a month for 2 months, followed by 81 mg BCG once a month as one cycle for three cycles. The primary endpoint was disease-free interval. Analyses were done by intention to treat. Results: Median follow-up was 121 months (IQR 70.5–163.5). Patients assigned sequential BCG and electromotive mitomycin had higher disease-free interval than did those assigned BCG alone (79 months [95% CI 27–139] vs 26 months [11–113]; difference between groups 53 months [39–67], log-rank p=0.0002). Patients assigned sequential BCG and electromotive mitomycin also had lower recurrence (45% [35–55] vs 62% [50–72], difference between groups 17% [6–28], log-rank p=0.0002); progression (12% [3–21] vs 28% [17.5–38.5], difference between groups 16% [5–27], log-rank p=0.003); overall mortality (44% [33–55] vs 59% [43–75], difference between groups 15% [2–28], log-rank p=0.01); and disease-specific mortality (9% [2.5– 15.5] vs 23% [11–34], difference between groups 14% [4–24], log-rank p=0.0055). Conclusions: In patients with high risk non-muscle invasive bladder cancer intravesical BCG combined with electromotive mitomycin provided better results than BCG alone in terms of higher remission rates and longer remission times.
Results of a phase II study of pralatrexate in patients with advanced/metastatic relapsed transitional cell carcinoma of the urinary bladder.
Authors: Loriot Yohann , Fizazi Karim , Carles Joan , Weems Garry Alan , Chance Lacey , Agarwal Neeraj 
Published: March 2020

4574 Background: Antifolate agents have demonstrated activity in transitional cell carcinoma (TCC), a disease with very poor outcomes in advanced stages. Pralatrexate (FOLOTYN, Allos Therapeutics, Inc., Westminster, CO), a folate analogue targeting dihydrofolate reductase, is designed for enhanced uptake and accumulation in tumor cells. The objective of this study was to examine the activity and safety of pralatrexate in patients (pts) with advanced/metastatic TCC of the urinary bladder after failure of prior chemotherapy. Methods: Pts with histologically confirmed TCC (>50% TCC in tumor) received pralatrexate 190 mg/m² intravenously on days 1 and 15 of a 28‑day cycle supplemented with vitamin B12 and folic acid. Included pts had Eastern Cooperative Oncology Group performance status of 0–1, measurable disease, and prior treatment with ≤1 platinum- and/or methotrexate-based regimen in the recurrent/metastatic setting. Results: Thirty pts were enrolled and treated. All pts received prior platinum-based therapy, and 7 pts (23%) received methotrexate in a multidrug regimen. One pt had a confirmed partial response (PR); 4 additional pts had unconfirmed PRs. Twelve pts had stable disease. The median number of cycles received was 2 (range, 1–24), and median time on treatment was 56 days (range, 1–714). The median progression-free survival (PFS) and overall survival for all pts was 4.0 months (95% confidence interval [CI], 2.1–4.5) and 9.3 months (95% CI, 5.6–13.2), respectively. Eight pts (27%) had PFS >6 months and 3 pts (10%) had PFS >12 months. Eight pts (27%) underwent dose reductions, all due to mucositis. Six pts (20%) discontinued the study due to treatment-related adverse events (AEs)—mainly mucositis. The most frequent treatment-related AEs were stomatitis (77%), asthenia (30%), vomiting (27%), and anemia, nausea, and neutropenia (23% each). Conclusions: Pralatrexate showed evidence of activity and durable disease control when used as a single agent in pts with advanced bladder cancer, although the overall response rate was modest. Further study of pralatrexate in this setting should focus on improving drug delivery and evaluation of novel combination approaches.
Long-term progression-free survival (PFS) and overall survival (OS) to pemetrexed (P) as single agent in metastatic urothelial carcinoma (MUC): A Spanish Oncology Genitourinary Group (SOGUG) systematic review.
Authors: Cervera Grau J. M. , Gonzalez-Billalabeitia Enrique , Ayala Francisco , Ballester Navarro Inmaculada , Lopez Antonio , Garde Javier , Juan Vidal Oscar , Satre Jose Manuel , Barrajon Enrique , Esquerdo Gaspar , Molins Carmen , Maciá Sonia , Rolfo Christian Diego , Espinoza Venegas Macarena Paz 
Published: March 2020

4587 Background: The effect of pemetrexed in MUC is not well characterized. Vinflunine is the standar second-line in MUC with adjusted benefits and no more drugs have been aproved. SOGUG reports a systematic review of MUC patient series with high activity of P in monotherapy. Methods: Patients with locally advanced urothelial carcinoma and/or MUC whom received P 500 mg/m(2) every 21 days with folic acid and vitamin B12 supplementation, were elected. These patients received P in second, third or fourth-line of chemotherapy. Results: 44 patients have been reported (39males), median age 62 [41-82]. Of all 44 patients; 21, 22, and 1 patients received P as second-line, third and fourth-line respectively. A median of 4 courses were administered [1-12] and disease control (SD+PR+CR) was achieved in 19 patients for an overall control rate of 43.2%. Four groups with significant differences in PFS (p=.033) were established (1.bone-metastasis, 2.visceral-metastasis, 3. nodal-visceral-metastasis and 4.nodal-metastasis). OS was significant between 2nd and 4th group (p=.036) . Mean PFS and OS were 125days [17-606] and 219days [17-1168] respectively for all 44 patients. Mean PFS and OS of 8 patients with bone metastasis were 75 days and 134 days. Mean PFS and OS of 10 patients with visceral metastasis were 65 days and 144 days. Mean PFS and OS of 8 patiens with nodal+visceral metastasis were 154 and 228 days. Mean PFS and OS of 18 patients with nodal metastasis were 166 days and 299 days. Conclusions: Our longer and multicenter follow-up shows that single agent P in monotherapy as second, third and fourth line in MUC is associated with high activity and long-time survival specially in metastatic nodal MUC. These results suggest that P as monotherapy requires to be further studied, more patients are being collected.
Correlation of chromosome (Chr) 14 loss and 5q gain with outcomes of pazopanib treatment in patients (pts) with metastatic clear cell renal cell carcinoma (mRCC).
Authors: Hudes Gary R. , Pei Jianming , Liu Yuan , Gagnon Robert C. , Carpenter Christopher , Pandite Lini , Testa Joseph 
Published: March 2020

4605 Background: The identification of molecular prognostic and/or predictive determinants of outcome in pts with mRCC is an important challenge. We hypothesized that specific tumor DNA copy number alterations (CNAs) - loss of chr 14 or 14q (14/14q-), and gain of chr 5q (5q+) may predict likelihood of pazopanib treatment benefit in pts with mRCC. Methods: Pts DNA samples from the Phase II (VEG102616) pazopanib trial were analyzed by using Affymetrix OncoScan. Copy no. data were moving smoothed and normalized. The copy no. and allele difference were profiled according to their chromosome locations to interrogate CNA and LOH. Objective response (OR, RECIST) and progression free survival (PFS) were determined by investigators (IN) and an independent review (IR) committee. OR and PFS data were analyzed using exact and Kaplan-Meier tests. Results: Tumor DNA samples from 75 pts were adequate for CNA analysis. 14/14q- was found in 35/75 pts (46.7%), and 5q+ was found in 37/75 (49.3%). 14/14q- was present in the tumors of 12/31 pts (39%) with OR by IR compared with 23/44 (52%) nonresponding pts (p=0.347). 14/14q- did not affect PFS. 5q+ was present in tumors of 17/31 pts (55%) with OR and 20/44 (45%) nonresponding pts (p=0.486). PFS was longer in pts with 5q+ tumors compared with those without 5q+ (log rank p=0.026), with median PFS of 66 vs 35 wks, respectively. The odds of achieving OR decreased as the total number of chromosomal gains/losses increased (p=0.032, odds ratio 0.49), but this had no effect on PFS. In exploratory analysis, we examined the combined effect of both 14/14q- and 5q+ on PFS (Table). Conclusions: Pts with 5q+ tumors have significantly longer PFS, with no effect on OR rate. While 14/14q- alone had no effect on outcomes, the combination of 5q+ and no 14/14q- was associated with significantly greater PFS. Pts with more genetically complex tumors were less likely to obtain OR with pazopanib. [Table: see text]
Selecting renal cell carcinoma therapy: Ranking of patient perspective on toxicities.
Authors: Wong Michael K.K. , Mohamed Ateesha F , Hauber A. Brett , Yang Jui-Chen , Liu Zhimei , Rogerio Jaqueline Willemann , Garay Carlos A. 
Published: March 2020

4608 Background: Oral therapies (angiogenesis inhibitors and mammalian target of rapamycin (mTOR) inhibitors) for renal cell carcinoma (RCC) have demonstrated significant improvements in progression-free survival but also possess toxicities. The objective of this study was to evaluate whether different toxicities of oral RCC therapies had equal importance to patients. Methods: US adults from the Kidney Cancer Association with a self-reported diagnosis of RCC completed a web-enabled survey. Respondents were asked to select the 3 most and 3 least troublesome toxicities from a list of 20 common RCC therapy toxicities. For each respondent, a value of 1 was assigned to each of the 3 most troublesome toxicities, a value of -1 was assigned to each of the 3 least troublesome toxicities, and a value of 0 was assigned to the remaining toxicities. A straight count method was applied to estimate the mean relative importance of each toxicity. Respondents also answered 10 treatment-choice questions, each of which included a pair of hypothetical RCC medication profiles described by survival, toxicities, and serious adverse events. Four toxicities including fatigue, mouth sores, hand-foot syndrome, and stomach problems were included in both exercises. Results: 264 of the 272 respondents completed the entire ranking exercise. Among the 20 toxicities, stomach problems was the most troublesome and was assigned an importance of 10. Changes in hair color was the least troublesome and was assigned an importance of 0. Patients ranked fatigue (8.2), mouth sores (7.7), hand-foot syndrome (6.6) by order of importance. When given choices among eliminating severe toxicities, fatigue was as important as stomach problems, both fatigue and stomach problems were more import than mouth sores, and mouth sores was more important than hand-foot syndrome; although not statistically significant. Conclusions: This statistical approach offers insight into those toxicities important to patients on chronic RCC therapies.