bluuebunny/crossref_metadata_2025_split huggingface dataset:
An open-label, multicenter, phase IIIb study of patients with urinary tract carcinoma (UTC) (STRONG): Interim safety results for fixed-dose durvalumab (D) monotherapy (module A).
Authors: Sonpavde Guru , Sternberg Cora N. , Lee Jae-Lyun , Palhares de Miranda Paulo Andre , Lima Ana Rita , Sarkeshik Makan , Hotte Sebastien J. 
Published: February 2020

484 Background: Patients (pts) with advanced UTC who fail first-line therapy have a poor prognosis and limited treatment options, with only modest benefit from chemotherapy. D (anti-PD-L1 antibody) is approved for the treatment of metastatic urothelial carcinoma after progression on platinum-based chemotherapy. Methods: Module A of the phase IIIb STRONG study (NCT03084471) will determine the short- and long-term safety of a fixed dose of D monotherapy (1500 mg, every 4 weeks) in pts with urothelial and non-urothelial carcinoma of the UT who progressed on or after prior chemotherapy. The primary endpoint is to determine the number of pts with adverse events of special interest (AESIs). This analysis included AEs with onset date on or after the date of first dose and up to 90 days after discontinuation of study treatment. Interim results from module A are reported. Results: A total of 700 pts received D monotherapy. Median age was 68.2 yr and 79.6% were male; 88.6% had an ECOG PS 0 or 1 and 11.3% an ECOG PS 2. Most (88.4%) had urothelial (transitional cell) carcinoma. Tumor PD-L1 expression was high (tumor or immune cell membrane positivity ≥25%) in 183/436 (42%) pts with PD-L1 data. Median treatment duration was 11.7 weeks (range, 1-73). AEs of any grade were reported in 86.9% of pts (Table), and in 89.0%, 86.9%, and 78.5% of pts with ECOG PS 0, 1, or 2, respectively. The most common grade ≥3 AESI was increased lipase (1.4%). Deaths related to study treatment occurred in 10 pts (1.4%). Conclusions: Fixed-dose D monotherapy has an acceptable safety profile as second-line therapy for UTC. Long-term safety data reported here are consistent with published studies of D monotherapy. Clinical trial information: NCT03084471.
Durvalumab as neoadjuvant therapy for muscle-invasive bladder cancer: Preliminary results from the Bladder Cancer Signal Seeking Trial (BLASST)-2.
Authors: Wei Xiao X. , McGregor Bradley Alexander , Lee Richard J. , Gao Xin , Kilbridge Kerry L. , Preston Mark A. , Mossanen Matthew , Ingham Matthew D. , Steele Graeme S. , Klein Alyssa , Van Allen Eliezer Mendel , Severgnini Mariano , Giannakis Marios , Sonpavde Guru 
Published: February 2020

507 Background: There is no established neoadjuvant therapy (NAT) for patients (pt) with muscle invasive bladder cancer (MIBC) ineligible for cisplatin-based chemotherapy preceding radical cystectomy. Encouraging prospective data indicate PD-1/PD-L1 inhibitors, including pembrolizumab and atezolizumab, are safe and active as NAT for MIBC. Durvalumab (D), a PD-L1 inhibitor, is FDA approved for treating locally advanced or metastatic urothelial carcinoma following platinum-based chemotherapy. The safety and activity of D as NAT in MIBC have not been reported. Methods: We are conducting a single-center sequential multicohort trial (NCT03773666) of D alone (Cohort 1, N=10) and D plus the CD73 inhibitor oleclumab (Cohort 2, N=10) in cT2-T4aN0M0 MIBC pts who are RC candidates and are ineligible for or declined cisplatin-based chemotherapy. The primary endpoint is feasibility, defined as ≥7 of 10 pts receiving at least 1 dose of D followed by radical cystectomy without dose limiting toxicity (DLT) up to 12 wks post-RC. In Cohort 1, D is administered at 750mg IV Q2W for 3 cycles followed by RC 2-4 weeks after the last dose. Baseline and RC tissue and baseline and on-study blood are collected for correlative studies, including immunohistochemistry, genomics, transcriptomics, and metabolomics. Results: Cohort 1 has completed enrollment; ten pts were enrolled between Feb 2019 to Sept 2019. Median age was 67 (Range: 53-85) and 8 (80%) were men. All 10 pts completed 3 durvalumab doses. Eight pts completed planned RC with at least 12wk follow-up post-op to date. No DLTs were observed. One Grade 3 treatment-related adverse event (trAE) was reported (anemia), with no Grade 4 or higher trAE. Pathologic response (<pT2N0) was seen in 2 of 8 (25%) pts with pathologic complete response (pT0) in 1 (12.5%) pts. Updated safety and efficacy data from Cohort 1 will be presented. Conclusions: D appears to be feasible as NAT in MIBC with preliminary evidence for antitumor activity. Toxicities are consistent with data from other PD-1/PD-L1 inhibitor trials. Future cohorts will examine D-containing combination NAT strategies. Analysis of tissue and blood-based predictive biomarkers are ongoing. Clinical trial information: NCT03773666.
Association of the Lung Immune Prognostic Index with outcome in patients with metastatic urothelial cancer treated with immune checkpoint inhibitor.
Authors: Pauline Parent , Auclin Edouard , Mezquita Laura , Chanza Nieves M. , Dumont Clement , Rodriguez-Vida Alejo , Lozano Rebeca , Vera Beatriz , Ratta Raffaele , Baciarello Giulia , Colomba Emeline , Fuerea Alina , Besse Benjamin , Loriot Yohann , Lavaud Pernelle 
Published: February 2020

545 Background: Prognostic factors for survival in metastatic urothelial carcinoma (mUC) have been reported in patients (pts) treated with chemotherapy (Bellmunt and al, JCO 2010). However, no biomarkers have been clearly identified in the setting of immune-checkpoint inhibitors (ICI). The Lung immune prognostic index (LIPI) was associated with clinical outcomes for ICI in lung cancer (Mezquita et al, Jama Oncol 2018) and other tumor types (Varga et al, TAT 2019). In this multicenter retrospective study, we correlated LIPI with outcomes in pts with mUC treated with ICI. Methods: Pts with mUC enrolled from May 2013 to July 2018 in 7 high volume centers were analysed. LIPI score includes: LDH > upper limit of normal and neutrophil/[leukocytes minus neutrophils] ratio (dNLR) > 3. The following LIPI subgroups were defined: good prognosis (0), intermediate prognosis (1) and poor prognosis (2 factors). Median (m) progression-free survival (PFS) and median overall survival (OS) were calculated using Kaplan-Meier method, log rank test was used for statistical comparison. Cox model was used for multivariate analysis. Results: To date, 152 mUC pts have been enrolled and preliminary analysis have been performed in 135 pts. Median age was 67 years, 111 (82%) pts were male, 106 pts (79%) had ECOG PS 0-1, 31 pts (23%) had liver metastasis. Median follow-up was 21.1 months (mo) (95% CI; 16.3-24.5), mPFS was 3.6 mo (95% CI; 2.6-6.0) and mOS was 13.8 mo (95% CI; 11.5-23.2). LIPI classified the population in good (56%), intermediate (35%) and poor (9%) prognosis group. In multivariate analysis, estimated mPFS in good, intermediate and poor prognosis were 5.8 mo (95% CI; 2.6-6.0), 3.6 mo (95% CI; 3.3-16.2) and 1.2 mo (95% CI;0.1-NR), respectively (p = 0.001). Estimated mOS in good, intermediate and poor prognosis were 17.3 mo (95% CI; 13.0-36.8), 16.9 mo (95% CI; 6.9-NR) and 5.4 mo (95% CI;2.5-NR), respectively (p = 0.19). OS data will be validated on larger cohort. Conclusions: The LIPI score is associated with clinical outcome to ICI and may be a useful tool for identifying patients who may not benefit from ICI. Validation in independent prospective cohort is ongoing.
IMvigor130 clinical trial in patients (pts) with metastatic urothelial carcinoma (mUC): Analysis of upper tract (UT) and lower tract (LT) subgroups.
Authors: De Santis Maria , Grande Enrique , Mencinger Marina , Li Jian-Ri , Puente Javier , Izumi Kouji , Lee Jae-Lyun , Kose Fatih , Antonyan Igor , Ding Beiying , Patel Himika , Davis Ian D. 
Published: February 2020

551 Background: IMvigor130 demonstrated a statistically significant improvement in PFS in pts receiving atezolizumab (atezo; anti–PD-L1) + platinum-based chemotherapy (plt/gemcitabine [gem]; Arm A) vs placebo + plt/gem (Arm C) as first-line treatment for mUC (Grande et al. 2019). Exploratory analyses examined efficacy outcomes in UT and LT mUC subgroups. Methods: Pts with UT and LT mUC from Arm A and Arm C were included. Chemotherapy was gem + investigator choice of plt (cisplatin or carboplatin). Tumors were assessed at baseline and every 9 wk until investigator-assessed PD per RECIST 1.1 or other events. PFS, OS and ORR in UT and LT subgroups are shown. Results: Baseline characteristics were comparable between Arm A and Arm C in the UT and LT subgroups; however, slight imbalances were noted, such as higher PD-L1–positive status (IC2/3) and lower Bajorin risk score in UT Arm A pts. With a median follow-up of 11.8 mo, median PFS was8.2 vs 6.2 mo in Arm A vs Arm C in UT pts (HR, 0.69 [95% CI: 0.51, 0.94]) and 8.1 vs 6.5 mo, respectively, in LT pts (HR, 0.85 [95% CI: 0.70, 1.02]). Interim median OS was 16.9 vs 13.5 mo in Arm A vs Arm C in UT pts (HR, 0.78 [95% CI: 0.54, 1.12]) and 15.8 vs 13.4 mo, respectively, in LT pts (HR, 0.87 [95% CI: 0.70, 1.08]). See table for additional efficacy results. Conclusions: Exploratorysubgroup analyses suggest activity of atezo + plt/gem in both UT and LT mUC, with outcomes in UT pts comparable to those seen in the LT and ITT populations. Clinical trial information: NCT02807636. [Table: see text]
Impact of early identification of brain metastases in metastatic renal cell carcinoma (mRCC).
Authors: Parmar Ambika , Ghosh Sunita , Lalani Aly-Khan A. , Hansen Aaron Richard , Reaume M. Neil , Wood Lori , Basappa Naveen S. , Heng Daniel Yick Chin , Graham Jeffrey , Kollmannsberger Christian K. , Soulieres Denis , Breau Rodney H. , Tanguay Simon , Kapoor Anil , Pouliot Frederic , Bjarnason Georg A. 
Published: February 2020

620 Background: Up to one-third of patients with mRCC can present with asymptomatic brain metastases (BM). Timely identification of BM allows for the delivery of early local interventions, which may lead to improved patient outcomes. To investigate the potential utility of routine intra-cranial imaging, we compared the outcomes of mRCC patients with asymptomatic versus symptomatic BM. Methods: Using the Canadian Kidney Cancer information system (CKCis) database, we identified mRCC patients diagnosed with BM between 2011 and 2018. This cohort was divided into two groups dependent on the presence or absence of neurological symptoms. Baseline patient demographics, clinico-pathological disease characteristics and survival data were extracted. Statistical analysis was through chi-square tests, analysis of variance and Kaplan-Meier method to characterize survival outcomes. Results: 269 mRCC patients with BM were identified with the majority presenting with symptomatic disease (n=163; 61%). No significant differences in clinico-pathological disease characteristics were identified. Median overall survival (OS) from mRCC diagnosis for asymptomatic patients was 33.4 months (interquartile range, IQR 27.8-64.4) versus 34.5 months (20.4-43.4) for symptomatic patients (p=0.35). Median OS from time of BM diagnosis revealed a trend favoring asymptomatic, as compared to symptomatic, patients [24.5 (17.6-24.9) vs. 13.1 months (9.0-20.6), p=0.06]. Factors associated with worse OS from time of BM diagnosis included presentation with symptomatic BM [hazard ratio, HR (95% CI): 1.40 (1.03-1.90), p=0.034] and International Metastatic Renal Cell Carcinoma Consortium Database (IMDC)-characterized intermediate/poor risk disease [HR (95% CI): 1.47 (1.01-2.13), p=0.045]. Conclusions: Routine intra-cranial imaging may lead to earlier identification of BM in mRCC. However, further investigation as to whether this practice improves survival is warranted.
Outcomes of patients with pancreatic-only oligometastatic renal cell carcinoma (RCC).
Authors: Duarte Cassandra , Martinez Chanza Nieves , Collier Katharine , Dizman Nazli , Rathi Nityam , McKay Rana R. , Panian Justine , Narayan Vivek , Carneiro Benedito A. , Mega Anthony E. , Hu Junxiao , Meguid Cheryl , Agarwal Neeraj , Pal Sumanta K. , Mortazavi Amir , Harshman Lauren Christine , Lam Elaine Tat 
Published: February 2020

681 Background: Patients (pts) with RCC and oligometastatic pancreas metastases are treated with pancreatectomy, stereotactic body radiation therapy (SBRT), or systemic therapy. The optimal approach is not clear. We aimed to evaluate the comparative efficacy of the modalities in terms of progression-free survival (PFS) and overall survival (OS). Methods: This IRB-approved, multi-institutional, retrospective study evaluated pts with pancreatic-only RCC metastasis without concurrent metastases elsewhere. Data on pt demographics, tumor characteristics, treatment, and outcomes were collected. PFS and OS in pts treated with pancreatectomy vs. systemic therapy were compared by log rank tests. Results: Fifty-one pts from 9 institutions were included. All had clear cell RCC; 50 pts had nephrectomy; 30 pts (58.8%) and 18 pts (35.3%) had IMDC favorable and intermediate risk, respectively. Median time from RCC diagnosis to oligometastatic disease was 120 months (mo) (range: 0, 175). As initial treatment, 23 (45%) pts had pancreatectomy (mostly partial); 25 (49%) had systemic therapy (VEGFR TKI and/or immunotherapy); 1 had SBRT; 2 had other treatments. Too few pts had SBRT for comparison. With a median follow-up of 25 mo (2, 68), median PFS for the population was 25 mo (17, 42 95% CI). Median PFS was 36 mo (8, 43 95% CI) for surgery pts and 22 mo (17, NR 95% CI) for systemic therapy pts; this was not statistically significant (NS), p = 0.3. Median OS for the population was 121 mo (100, NR 95% CI). With a median follow-up of 51 mo (2, 217), OS was 121 mo (100, NR 95% CI) for surgery pts and not reached (64, NR 95% CI) for systemic therapy pts; NS, p = 0.52. Conclusions: In this retrospective series, RCC pts with oligometastatic pancreatic-only disease had similar PFS and OS outcomes from initial pancreatectomy or systemic therapy. RCC pts with pancreas-only metastases represent a unique patient population and studies informing the underlying biology are needed to optimize clinical management.
A comparison of combined immune checkpoint inhibitors (IO) versus vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKI) in the treatment of advanced clear cell renal cell carcinoma.
Authors: Chan Abigail Sy , Pond Gregory Russell , Sonpavde Guru , Alva Ajjai Shivaram 
Published: February 2020

692 Background: IO and VEGFR/TKI are approved treatment options, either alone or combination, in advanced clear cell RCC. Currently, there is a lack of evidence comparing efficacy and safety outcomes amongst these therapies. We sought to compare the published data for the various options with respect to efficacy and safety. Methods: A literature search using PubMed, clinicaltrials.gov, ASCO and ESMO meeting abstract databases from January 1, 2015 to June 30, 2019 to identify eligible clinical trials in advanced clear cell RCC involving at least one immunotherapy agent was performed. Due to small sample sizes in the various cohorts, descriptive statistics were provided. Weighting of estimates was based on sample size of the intervention arms. Results: 14 studies involving 6,197 pts were identified. The median age was 62 years (54.8, 64), men constituting median of 75%, and prior TKI receipt in 63%. There were 7 studies in each treatment arm. The efficacy outcomes did not demonstrate statistical differences. In the safety analyses, IO + VEGFR/TKI demonstrated the highest serious adverse event rate, correlating with treatment discontinuation rates. Conclusions: IO + IO and IO + VEGFR/TKI showed comparable efficacy and toxicity outcomes in the treatment of advanced clear cell RCC. There is a non-significant trend towards increased efficacy in some outcomes with IO + VEGFR/TKI, with possibly increased adverse events. Further studies with patient level data, cross-comparative trials, and predictive biomarkers are needed to establish a therapeutic matrix for RCC pts.[Table: see text]
Molecular characteristics of renal cell carcinoma (RCC) risk groups from JAVELIN Renal 101.
Authors: Choueiri Toni K. , Haanen John B. A. G. , Larkin James M. G. , Rini Brian I. , Albiges Laurence , Motzer Robert J. , di Pietro Alessandra , Mu Xinmeng Jasmine , Ching Keith A. , Hariharan Subramanian , Robbins Paul B. 
Published: February 2020

744 Background: The phase 3 JAVELIN Renal 101 trial in patients (pts) with advanced RCC demonstrated a progression-free survival (PFS) benefit and higher objective response rate (ORR) with avelumab + axitinib (A+Ax) vs sunitinib (S) (Motzer NEJM 2019). PFS and ORR favored A+Ax in all MSKCC risk groups, but median PFS varied. Here, we report results from analyses of baseline tumor samples to define molecular characteristics underlying risk group classifications. Methods: Nephrectomy or tumor samples from pts enrolled in the study were characterized by immunohistochemistry (CD8 and PD-L1), whole exome sequencing, or gene expression profiling (n = 705–850). Gene expression signatures (GES), pathway activation status, and mutational profiles were examined in relation to MSKCC risk groups. Results: Of the 886 total pts enrolled, 23%, 66%, and 11% had favorable (F), intermediate (I), or poor (P) MSKCC risk factors at baseline. In the F, I, and P groups, the ORR was 66%/38%, 50%/24%, and 31%/9%; median PFS was NR/16.7 mo, 13.3 mo/7.9 mo, and 5.6 mo/2.8 mo for the A+Ax/S arms, respectively. Neither the presence of PD-L1+ immune cells nor CD8+ cells differentiated the subgroups; however, the presence of PD-L1+ tumor cells was highest in the P group (p=0.0159). When compared to the I and P groups, the F group was enriched for NOTCH2 mutations (p=0.0002), displayed high FLT1 expression (p=0.007), and showed a trend favoring angiogenesis GES (JAVELIN Renal 101 and IMmotion150). The I group displayed few distinguishing characteristics (low neutrophil GES [p=0.02] and elevated homeobox gene expression [p=0.00052]). Relative to the F group, the P group showed higher cell cycle gene expression (p=0.0057) and PTEN mutation frequency, wild-type NOTCH2 genotype, elevated IMmotion150 Myeloid inflamed GES (p=0.0024), and macrophage-specific GES (p=0.0327), as well as GES for TH2 (p=0.0002), hypoxia (p=0.0199), glycolysis (p=0.0066), and the lowest expression of a dendritic cell GES (p=0.0209). Conclusions: In advanced RCC patients, biological differences within each MSKCC risk category may impact response to treatment and may help explain why these groups perform differently. Clinical trial information: NCT02684006.
Oligopelvis-GETUG P07: A multicenter phase II trial of combined salvage radiotherapy and hormone therapy in oligorecurrent pelvic node relapses of prostate cancer.
Authors: Supiot Stephane , Pasquier David , Buthaud Xavier , Magné Nicolas , Beckendorf Veronique , Sargos Paul , Crehange Gilles , Pommier Pascal , Loos Genevieve , Hasbini Ali , Latorzeff Igor , Silva Marlon , Denis Fabrice , Lagrange Jean-Leon , Campion Loic , Vaugier Loig , Blanc-Lapierre Audrey 
Published: February 2020

93 Background: Oligorecurrent pelvic nodal relapse of prostatic cancer is a challenge for regional salvage treatments. We conducted OLIGOPELVIS – GETUG P07, a phase II trial of combined salvage radiotherapy and hormone therapy in oligorecurrent pelvic node relapses of prostate cancer (NCT02274779). Methods: OLIGOPELVIS–GETUG P07 was a prospective multi-center phase II trial investigating high-dose salvage pelvic irradiation with an additional dose to the fluorocholine-based positron-emission-tomography (FCH- PET)-positive pelvic lymph nodes (PLN), combined with six-month androgen blockade (LH-RH agonist or antagonist injections). The prescribed dose was 54 Gy in 1.8 Gy fractions with up to 66 Gy in 2.2 Gy fractions to the pathological PLN. Toxicity (CTCAE v4) and complete response rates (PSA < 0.20 ng/ml) were analyzed. The main objective was to assess biochemical-clinical failure defined by a cluster of events including PSA progression (≥25 % and ≥ 2 ng/ml above the nadir) or clinical evidence of local or metastatic progression or post- treatment initiation of hormonal therapy or prostate cancer-related death. We hypothesized that salvage treatment would achieve a 2-year relapse-free survival of 70 %. Results: Seventy-four patients were recruited in fifteen French radiation oncology departments between August 2014 and July 2016. Seven were excluded before treatment because of violation of the inclusion criteria. The intention-to-treat analysis therefore included sixty-seven patients. Half of them had received prior prostatic/prostate bed irradiation. Median age was 67.7. Grade 2+ two-year urinary and intestinal toxicity were 10% and 2% respectively. At 2 and 3 years, 73.1 and 45.9% of patients achieved a persisting complete response respectively. After a median follow-up of 34 months, the 2-year progression-free survival rate was 77.6%. Median progression-free survival was 40.1 months. Conclusions: Combined pelvic salvage radiotherapy and hormone therapy allowed for prolonged tumor control in oligorecurrent pelvic node relapses of prostate cancer with limited toxicity. Clinical trial information: NCT02274779.
Chemokine signaling and MAPK/ERK pathway for advanced prostate cancer treatment response.
Authors: Numan Yazan , Zhao Jonathan , Tang Song , Zhang Youbin , Zhang Qiang , Jovanovic Borko , VanderWeele David James , Morgans Alicia K. , Cristofanilli Massimo , Yu Jindan , Hussain Maha H. A. 
Published: February 2020

TPS275 Background: Androgen deprivation therapy (ADT) is the backbone of therapy for metastatic hormone sensitive prostate cancer (mHSPC). Despite a high response rate, the majority of patients progress to metastatic castration-resistant prostate cancer (mCRPC). Both disease settings are heterogeneous with variable responses to treatment. While prostate specific antigen is an important biomarker for prognosis and disease monitoring, it has limitations. Biomarkers predictive of disease response and progression are critically needed. Circulating tumor cells (CTCs) are shed from tumors and are found in blood during advanced stages of disease. Serial characterization of CTCs serves as a real-time ‘liquid biopsy’ for molecular profiling of PC. Recent reports suggest that phenotypic & genomic heterogeneity in CTCs and cell-free DNA (cfDNA) is associated with response to AR-targeted therapy highlighting the importance of CTC as a predictive biomarker. In addition, there is a high concordance between mutations in CTCs’ DNA and CRPC tissue through whole cell exome sequencing. We showed that atypical chemokine receptor CXCR7 is up-regulated following AR-targeted therapies, activating MAPK/ERK signaling and resulting in treatment resistance (Li et al., Cancer Res. 2019). To examine the potential of CXCR7/MAPK/ERK signaling in predicting treatment response, we propose to evaluate MAPK/ERK gene signature, pERK and AR level in CRPC or mHSPC patients receiving systemic therapy. Methods: Men with new CRPC or mHSPC are eligible prior to initiating new therapy for the respective disease setting of ADT + AR targeted therapy or chemotherapy. For CRPC arm, we will collect samples at baseline, 3, 6 months & at time of progression. For mHSPC arm, samples are collected at baseline, after 7 months & at progression. We will enroll 120 patients. Collected samples are subjected to identification, isolation, and enumeration of CTCs. Our primary molecular testing will include AR and pERK staining. CfDNA exome and methylome analysis will be performed to evaluate genomic heterogeneity and epigenomic alterations. We will explore pairwise association among biomarkers of interest, stratified by subgroups, using measures of association.