tbuckley/cabot-search huggingface dataset:
A multicenter phase II study of low-dose erlotinib in frail patients with EGFR mutation-positive, non-small cell lung cancer: Thoracic oncology research group (TORG) trial 1425.
Authors: Kazuhiko Yamada, Shingo Miyamoto, Koichi Azuma, Hidenobu Ishii, Akihiro Bessho, Nobuaki Fukamatsu, Hideo Kunitoh, Mari Ishii, Hiroshi Tanaka, Hiromi Aono, Yoshiro Nakahara, Kei Kusaka, Yukio Hosomi, Norihiro Kikuchi, Yoshiaki Mori, Hidetoshi Itani, Takashi Kasai, Masao Ichiki, Nobuhiko Seki, Hiroaki Okamoto
Journal: Journal of Clinical Oncology (2018)

9063 Background: We previously reported that low-dose erlotinib has a certain degree of efficacy with lower toxicity in patients with non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations (Eur J Cancer 2015). This multicenter phase II study was undertaken to investigate the efficacy and safety of low-dose erlotinib for those patients with frailty. Methods: Chemotherapy-naïve NSCLC patients with EGFR mutations who had frailty were enrolled and received erlotinib 50 mg/d. Dose escalation was allowed to those with stable disease after 4 weeks. Patient’s frailty was defined as follows: (Group 1) 20 to 74 years of age with Eastern Cooperative Oncology Group performance status (PS) ≥2 or Charlson Comorbidity Index (CCI) ≥6 points; (Group 2) 75 to 80 years of age with PS ≥1 or CCI ≥6 points; (Group 3) ≥81 years of age with any PS and CCI. The primary endpoint was independent review committee (IRC)-confirmed objective response rate (ORR) to the low-dose erlotinib, with target ORR of 65% and threshold of 50% (SWOG two-stage design). Results: Eighty patients were enrolled between December 2014 and April 2017: males/females 26/54; median age 80 (range 49-90); Group 1/2/3 15/28/37; Ad/Sq/Others 76/1/3. EGFR mutation types were: exon 19/21 42/38. All 80 patients were included in efficacy and safety analysis. The IRC-confirmed ORR was 60.0% (90%CI: 50.2-69.2%), and the primary endpoint was met. The disease control rate was 86.3% (90%CI: 78.3-92.1%). Median progression-free survival was 9.2 months. Although overall survival data are immature, median survival time and 1-year survival rate were 26.3 months and 68.9%, respectively. Toxicities were generally mild, with a few grade 3 or more toxicities. There was no case of interstitial lung disease or treatment-related death. Conclusions: This is the first prospective study evaluating low-dose erlotinib for frail patients with EGFR mutation-positive NSCLC. Low-dose erlotinib is active and could be a treatment option for those patients. Clinical trial information: UMIN 000015949.
Quality of life (QOL) to predict overall survival (OS) in women with platinum-resistant ovarian cancer (PROC).
Authors: Felicia Roncolato, Emma Gibbs, Chee Lee, Lucy Claire Davies, Val Gebski, Michael Friedlander, Felix Hilpert, Lari B. Wenzel, Martin R. Stockler, Madeleine Trudy King, Eric Pujade-Lauraine
Journal: Journal of Clinical Oncology (2016)

5575 Background: Women with PROC are a heterogeneous group with a median overall survival of 12 months. We hypothesised that QOL measures would be significant prognostic factors in PROC and improve predictions of survival based on clinical factors. Methods: Data from 333 participants in AURELIA, randomised phase 3 trial of chemotherapy +/- bevacizumab, was used to identify domains of QOL, measured at baseline with the EORTC QLQ-C30 & OV28, that were significantly associated with OS in Cox regression analyses. Cut-points were determined to categorise patients as low, medium and high risk groups. Multivariable analysis for categorised QOL domains significantly associated with OS was performed adjusting for established clinical prognostic factors. Cut-points were validated in an independent dataset, CARTAXHY, a randomised trial comparing different chemotherapies in PROC. Results: In AURELIA, physical functioning (PF), role, emotional, social, global health, and abdominal/gastrointestinal symptoms (AGS) scores were significantly associated with OS in univariable analyses. PF (P < 0.001) and AGS (P < 0.001) scores remained significant in multivariable models. When categorized into high (PF score < 67), medium (67-92), and low ( > 92) risks, mOS were 11.2, 14.7 and 19.3 months respectively (P < 0.001). These categories were applied in the CARTAXHY population (N = 136), and mOS were 7.9, 16.2 and 23.9 months (P < 0.001) respectively. For high (AGS score > 44), medium (13-44), and low ( < 13) risks, mOS were 11.9, 14.3, and 20.0 months in AURELIA (P < 0.001); and 10.5, 19.6, and 24.1 months in CARTAXHY (P = 0.001). PF (P = 0.048) and AGS (P = 0.011) remained independently significant prognostic factors after adjusting for performance status, ascites, CA125, platinum-free interval, primary platinum resistance, and size of measurable lesions. Conclusions: Self-ratings of physical functioning and abdominal/gastrointestinal symptom scores improved predictions of overall survival based on traditional clinical factors in PROC. This additional prognostic information could improve stratification in clinical trials, patient-doctor-communication about prognosis, and clinical decision-making. Clinical trial information: NCT00976911.
Randomized phase 2 trial of cediranib alone or cediranib plus lenalidomide in iodine 131-refractory differentiated thyroid cancer (DTC): A University of Chicago Phase 2 Consortium trial.
Authors: Jonas A. De Souza, Theodore Karrison, Bernadette Libao, Francis P. Worden, Monika Krzyzanowska, David N. Hayes, Eric Winquist, Vassiliki Saloura, Victoria Meucci Villaflor, Tanguy Y. Seiwert, Walter Michael Stadler, Ezra E.W. Cohen, Rebecca B. Schechter, Everett E. Vokes
Journal: Journal of Clinical Oncology (2016)

6013 Background: Single agent VEGFR inhibitors and lenalidomide (L) have shown activity in advanced DTC, but combination therapy has not been evaluated. The goal of this study was to determine progression-free survival (PFS) in DTC patients (pts) treated with cediranib (C) or cediranib plus lenalidomide (C+L). Methods: Pts were required to have DTC with evidence of measurable and progressive disease within 12 months of enrollment. One prior VEGF inhibitor treatment was allowed and used as a stratification factor. Following a Phase 1 trial, pts were randomized in a 1:2 ratio to C 30mg daily or C 30mg daily plus L 15mg days 1-21 (C+L) every 4 weeks. An interim analysis was to be performed based on PFS after half (40) of the expected number of events (80) occurred. Results: 110 pts were enrolled and randomized from 2010 to 2015. Two pts withdrew consent before receiving therapy and were considered non-evaluable, leaving 108 for analysis (39 C and 69 C+L). Median follow-up time was 9.9 months. Baseline characteristics were similar in the two arms. Mean ages (range) were 62 (27-86) and 64 (24-83) in the C and C+L arms, respectively; 23% of pts in both arms received prior VEGF therapy. Grade 2 or higher AE’s at least possibly related to the study drugs in C vs C+L arms were: diarrhea (15% vs 10%), fatigue (26% vs 25%), generalized weakness (0% vs 5.8%), hypertension (23% vs 22%), oral mucositis (7.7% vs 4.3%), neutropenia (2.6% vs 14%), hand and foot syndrome (15% vs 4.3%), and proteinuria (0% vs 7.2%). At the planned interim analysis, the median PFS was 21 months in the C arm and 11 months in the C+L arm. The trial was then discontinued for futility with a conditional power of less than 15%. After an additional 10 months of follow-up, the PFS remained higher in the group randomized to C alone: 1 and 2-year PFS rates of 58% and 28% (median 14 months) in the C arm vs. 45% and 14% (median 11 months) in the C+L group (logrank p=0.39). Overall survival (OS) was similar: 1 and 2-year OS of 82% and 62% in C vs. 84% and 66% in C+L (logrank p=0.60). Conclusions: Single therapy with the VEGFR inhibitor cediranib showed promise in DTC, while the addition of lenalidomide was associated with lower PFS. Clinical trial information: NCT01208051.
TCT-780 First Direct Comparison of the Self-expandable Portico versus the Balloon-expandable Sapien 3 Device for Trans-catheter Aortic Valve Replacement: a Case-matched Cohort Study
Authors: Silvia Mas-Peiro, Helge Weiler, Gina-Lisa Mohr, Nestoras Papadopoulos, Andreas Zeiher, Stephan Fichtlscherer, Mariuca Vasa-Nicotera
Journal: Journal of the American College of Cardiology (2018)
Phase 1 trial of pegzilarginase in patients (pts) with relapsed/refractory (R/R) AML or MDS refractory to hypomethylating agents (HMAs).
Authors: Geoffrey L. Uy, Michael R. Savona, Benjamin K. Tomlinson, Hetty Carraway, Dale L. Bixby, Sarit E. Assouline, Joseph M. Brandwein, Moshe Yair Levy, Robert Collins, Humberto Lara-Guerra, Susan Alters, Stephen Eckert, Scott Rowlinson, James Wooldridge, Aaron David Schimmer
Journal: Journal of Clinical Oncology (2018)

7031 Background: In vitro studies demonstrate that AML cells are arginine auxotrophs and are metabolically vulnerable to arginine depletion (PMID: 24018014 & 25896651). To test the clinical utility of arginine depletion in AML we performed a phase 1 trial of pegzilarginase, a pegylated, recombinant, cobalt-substituted, human arginase I in pts with R/R AML or MDS (NCT02732184). Methods: Pts with R/R AML or HMA-refractory MDS were enrolled in a phase 1 dose escalation study using a 3+3 design. The primary endpoint was MTD. Other endpoints included safety, PK, PD (arginine & ornithine), immunogenicity, preliminary clinical activity, and expression of ASS1, ASL, & OTC in blasts. Results: Twenty-one pts (19 AML, 2 MDS) were treated with weekly pegzilarginase 0.12 to 0.48 mg/kg. Low ASS1 expression was observed in the majority of pt samples by rtPCR. Eleven pts received at least 4 doses. One dose-limiting toxicity (DLT) of reversible G4 encephalopathy was observed at 0.48 mg/kg. Seven pts were then enrolled at 0.36 mg/kg. No DLTs were observed but 4 pts discontinued treatment before receiving 4 doses (3 - disease progression, 1 - withdrew consent). Related serious or ≥ Gr3 AEs in ≥2 pts were nausea and vomiting (3 pts each), and diarrhea and fatigue (2 pts each). Related AEs in ≥10% of pts included nausea (10 pts, 2 Gr 3), vomiting (9, 2 Gr 3), fatigue (7, 1 Gr 3), decreased appetite (6), diarrhea (3, 2 Gr 3), and dizziness (3, 1 Gr 3). The pegzilarginase t½ was ~39 to 49 hr at ≥ 0.24 mg/kg and depleted arginine to ~10% of baseline for ≥48 hrs. One of 14 pts developed a low titer of anti-drug antibodies 4 weeks after start of treatment that was no longer detected at end of treatment (3 weeks after last dose). No clinical responses were observed. Conclusions: Pegzilarginase was well tolerated up to 0.36 mg/kg with a manageable safety profile. PK/PD data support weekly dosing, as confirmed by a rapid and sustained reduction in blood arginine. The observed results are consistent with a recent Ph 2 trial of arginine depletion in AML (PMID:28900115), suggesting depletion of arginine alone is insufficient for clinical activity in AML. Alternative approaches including combination therapy may be required. Clinical trial information: NCT02732184.
Impact of the addition of bevacizumab, oxaliplatin or irinotecan to fluoropyrimidin in the first-line treatment of metastatic colorectal cancer in elderly patients.
Authors: Thierry Landre, Thomas Aparicio, Djamel Ghebriou, Patrick Nicolas, Cherifa Taleb, Kader Chouahnia, Laurent H. Zelek, Gaetan Des Guetz
Journal: Journal of Clinical Oncology (2017)

e15034 Background: The clinical benefit of double-front-line therapy (including oxaliplatin or irinotecan or bevacizumab plus 5FU or capecitabine) compared to monotherapy (5FU or capecitabine) in elderly ( &gt; 70 years) patients with metastatic colorectal cancer (MCRC) is controversial. We performed a meta-analysis of published randomized studies. Methods: The selection of the studies was carried out using PubMed with the following keywords: "metastatic colorectal cancer", "elderly", "oxaliplatin", "irinotecan", "bevacizumab", "survival". The efficacy endpoints were overall survival (OS) and progression-free survival (PFS). Hazard Ratios (HRs) with their 95% confidence intervals (CIs) were collected from the studies and pooled. By convention, a HR &lt; 1 was a result in favor of bitherapy. Results: This meta-analysis (MA) included nine studies: three assess irinotecan (FFCD 2001-02, CAIRO and an already published MA); three others assess oxaliplatin (FOCUS2, FFCD 2000-05 and FOLFOX pivotal trial) and the last three ones assess bevacizumab (AVEX, AGITG-MAX and AVF2192g). Our MA included 1600 patients (62% of men). Concerning age, we chose a cut-off of 70 years or a cut-off of 75 years, corresponding to the available data for each study. The performance index (PS) was 0-1 for about 90% of patients, with the exception of FFCD 2001-02 and FOCUS2 which included 30% of patients with PS2. Overall, the addition of bevacizumab to fluoropyrimidin statistically improved both OS and PFS (HR = 0.78; CI: 0.62–0.98 and HR = 0.51; CI: 0.41–0.64, respectively). The addition of oxaliplatin statistically improved PFS (HR = 0.81; CI: 0.67–0.97) but not OS (HR = 0.99; CI: 0.85–1.17) as well as the addition of irinotecan (HR = 0.83; CI: 0.68–1.00 and HR = 1.01; CI: 0.84–1.22, respectively). Conclusions: In previously untreated elderly patients with MCRC, the addition of bevacizumab to fluoropyrimidin appears more effective in terms of OS or PFS than the addition of oxaliplatin or irinotecan.
Abstract 17492: Associations of Penraxin 3 with Mortality After Stroke and White Matter Hyperintensities Volume
Authors: Wi-Sun Ryu, Chi Kyung Kim, Beom Joon Kim, Seung-Hoon Lee
Journal: Circulation (2010)

Objectives: Recent experimental studies have revealed that Pentraxin 3 (PTX3) is a novel inflammatory marker and has an important role in regulation of the inflammatory process. Furthermore, PTX3 has been associated with cardiovascular disease and mortality. We examined associations of PTX3, a vascular inflammatory marker, with mortality and white matter hyperintensities volume (WMHV) in patients with acute ischemic stroke. Methods: Blood samples were collected from 376 patients admitted to the stroke unit with ischemic stroke. PTX3 plasma concentrations and WMHV were measured by ELISA and quantitative method, respectively. The patients were divided into tertile according to levels of PTX3. We used Cox-regression analysis to examine hazard ratios (HR) and 95% confidence interval (CI) of tertiles of PTX3 for all-cause mortality and multiple linear regression to examine the independent association of log-PTX3 and log-transformed white matter hyperintensities volume. Results: During 4.6 years, 94 patients (2...
The European Respiratory Society: ensuring excellence through education best practice
Authors: Amy Farr, Mina Gaga, Tobias Welte, Thierry Troosters, Guy Joos, Carlos Robalo Cordeiro, O. Chris Burghuber, Guy Brusselle, Christina-Georgia Gratziou, Andrew Bush, Isabel Saraiva, Carine Pannetier, Daiana Stolz
Journal: European Respiratory Journal (2018)

<b>By following education best practices, using available technology to remove barriers and continuing to ensure content remains free from bias, @ERStalk is committed to guiding respiratory health professionals along the path of lifelong learning</b>http://ow.ly/4uUa30leLMb
Prognostic value of CXLC 9 in patients undergoing neoadjuvant radiochemotherapy and surgery in stage IIIA NSCLC.
Authors: Wolfgang Parsch, Ralph M Wirtz, Bettina Braunecker, Dieter Würflein, Clemens Albrecht, Dietmar Kraus, Thomas Papadopoulos, Joachim H Ficker, Wolfgang M. Brueckl
Journal: Journal of Clinical Oncology (2018)

e24156 Background: Neoadjuvant radiochemotherapy is an established strategy to downgrade and downsize locally progredient NSCLC to become curatively resected. Upon tumor regression tumor antigens become accessible to immune cells, which may trigger T-Cell dependent responses contributing to prolonged survival. Aim of the study was to analyse wether molecular markers indicating T-Cell infiltration may be predictive for survival from initial biopsies and resected tumors. Methods: 27 patients with stage IIIA NSCLC underwent neoadjuvant radiochemotherapy followed by curative resection (R0) at our Lung Cancer Centre between 2008 and 2014. For 15 patients of those pretherapeutical biopsies and the corresponding resected tumors could be analyzed for immunhistochemistry (PD-L1, CD...) and mRNA-based gene expression (PD-1, PD-L1, CXCL9) from FFPE slides. Additionally, clinical and follow-up data were available of all patients. For each marker and clinical parameter the study population was divided into two groups according to the median. Primary endpoint of this retrospective study was overall survival. Results: The minimal follow-up was until death or 38,4 months. Median survival was 28,3 months. In the group of patients with a high expression of CXCL9 in the diagnostic biopsy an extended overall survival was observed (39,0 months vs. 18,8 months; p = 0,021). The level of gene expression of PD-1 (32,9 months vs. 26,8 months; p = 0,613) and PD-L1 (33,3 months vs. 24,6 months; p = 0,336) did not reveal any prognostic relevance. A comparison of the groups based on immunhistochemistry parameters detected no relevant differences. Comparing matched tissue samples before and after neoadjuvant RCT revealed a significant decrease in CXCL9 levels upon complete remission (p = 0,03). In contrast PD-L1 levels were stable or frequently increased in non-responding tumours. Conclusions: These results suggest that CXCL9 expression could be of predictive and prognostic value for chemotherapy response and prolonged overall survival of patients undergoing neoadjuvant radiochemotherapy. Further prospective studies are necessary to evaluate this marker, especially in times of immunooncology.
The effect of pain self-management based on pain control diary on breakthrough pain.
Authors: Zu-Yan Fan, Jin-Xiang Lin, Xing Li, Xiang-Wei Chen, Xiu-Yan Huang
Journal: Journal of Clinical Oncology (2017)

10107 Background: Most patients suffer from cancer pain, especially breakthrough pain. The overall incidence of breakthrough pain is estimated to be 65%. Self-management makes patients actively participating in the use of drugs, transforming their roles and adjusting their moods in order to better cure their own diseases. Therefore, the aim of the study is to discuss the effect of reducing cancer pain patients' breakthrough pain through self-management based on pain control diary. Methods: From October, 2015 to October, 2016, a total of 200 patients treated with opioids for cancer pain were randomly divided into groups. Patients in the control group were given general management including the Standard "the three steps analgesic ladder treatment for cancer pain", the traditional form of health education and psychological care; While the intervention group in addition to conventional cancer pain management, self-management based on pain control diary was applied. Through repeated intensive training, patients learned how to do self-assessment, to master the feature of their own pain, problem-solving skills and formal report to their oncologists in charge. Results: After six weeks of intervention , 10% patients in the intervention group had suffer breakthrough pain compared with 54% patients in the control group (P &lt; 0.05). The whole processing management model is a whole process, specialization and humanization Care model for patients with advanced cancer pain management, can effectively improve patient medication compliance, reduce the cancer breakthrough pain's incidence, improve the patients,s life quality with cancer pain. The medication compliance of the intervention group was significantly higher than that of the control group(X 2 = 46.606, P&lt;0.001), and in intervention group the incidence of breakthrough pain was significantly lower than that of the control group (X 2 = 44.148, P&lt;0.001) Conclusions: The self management based on pain control diary is a whole process, specialization and humanization Care model for patients with advanced cancer pain management, can effectively improve patient medication compliance, reduce the cancer breakthrough pain's incidence, improve the patients's life quality with cancer pain.
Phase 3, randomized, double-blind, placebo-controlled study of venetoclax combined with azacitidine versus azacitidine in treatment-naïve patients with acute myeloid leukemia.
Authors: Jalaja Potluri, Tu Xu, Wan-Jen Hong, Mack H. Mabry
Journal: Journal of Clinical Oncology (2017)

TPS7069 Background: Elderly acute myeloid leukemia (AML) is a biologically and clinically distinct disease with a diminished response to chemotherapy, low remission rates, and short disease-free and overall survival. Venetoclax (VEN) is a potent, selective small-molecular inhibitor of BCL-2. In preclinical models, venetoclax has been shown to kill AML cells as a single agent with demonstrated synergistic activity in combination with the DNA methyltransferase inhibitor azacitidine (AZA). Early clinical data from a phase 1b study (NCT02203773) showed that VEN plus AZA had an acceptable safety profile and promising efficacy in treatment-naïve elderly patients with AML. The current phase 3 study continues to evaluate the combination for this AML population. Methods: This phase 3, randomized, double-blind, placebo-controlled study (NCT02993523) is designed to assess VEN plus AZA compared with placebo plus AZA in treatment-naïve elderly and adult patients with AML who are not eligible for standard induction therapy due to age or comorbidities. Primary objectives of the study are to evaluate if VEN with AZA will improve overall survival (OS) and composite complete remission rate (CR+CRi) versus placebo with AZA. Secondary objectives include event-free survival, CR+CRi rate at the end of Cycle 1, and if combining VEN plus AZA reduces fatigue and improves global health status/quality of life based on patient reported outcomes versus placebo with AZA. Exploratory objectives are to evaluate biomarkers predictive of VEN activity including minimal residual disease negativity rate, and BCL-2 expression and outcome measures of overall survival and complete remission rate, as well as the impact of VEN on additional quality of life measures. Patients will be randomized 2:1 to VEN plus AZA (arm A) or placebo plus AZA (arm B). Patients on arm A will receive once daily 400 mg VEN orally on days 1–28 plus daily 75 mg/m 2 SC or IV AZA for 7 days in a 28-day cycle. Patients on arm B will receive once daily placebo orally on days 1–28 plus daily 75 mg/m 2 SC or IV AZA for 7 days on a 28-day cycle. Study recruitment began in February 2017, with target enrollment of 400 patients. Clinical trial information: NCT02993523.
Anlotinib: a novel multi-targeting tyrosine kinase inhibitor in clinical development
Authors: Guoshuang Shen, Fangchao Zheng, Dengfeng Ren, Feng Du, Qiuxia Dong, Ziyi Wang, Fuxing Zhao, Raees Ahmad, Jiuda Zhao
Journal: Journal of Hematology & Oncology (2018)

Anlotinib is a new, orally administered tyrosine kinase inhibitor that targets vascular endothelial growth factor receptor (VEGFR), fibroblast growth factor receptor (FGFR), platelet-derived growth factor receptors (PDGFR), and c-kit. Compared to the effect of placebo, it improved both progression-free survival (PFS) and overall survival (OS) in a phase III trial in patients with advanced non-small-cell lung cancer (NSCLC), despite progression of the cancer after two lines of prior treatments. Recently, the China Food and Drug Administration (CFDA) approved single agent anlotinib as a third-line treatment for patients with advanced NSCLC. Moreover, a randomized phase IIB trial demonstrated that anlotinib significantly prolonged the median PFS in patients with advanced soft tissue sarcoma (STS). Anlotinib also showed promising efficacy in patients with advanced medullary thyroid carcinoma and metastatic renal cell carcinoma (mRCC). The tolerability profile of anlotinib is similar to that of other tyrosine kinase inhibitors that target VEGFR and other tyrosine kinase-mediated pathways; however, anlotinib has a significantly lower incidence of grade 3 or higher side effects compared to that of sunitinib. We review the rationale, clinical evidence, and future perspectives of anlotinib for the treatment of multiple cancers.