Institution
Hebron University
Education•Hebron, Palestinian Territory•
About: Hebron University is a education organization based out in Hebron, Palestinian Territory. It is known for research contribution in the topics: Population & Cancer. The organization has 2714 authors who have published 4180 publications receiving 163736 citations.
Topics: Population, Cancer, Breast cancer, Medicine, Metastatic breast cancer
Papers published on a yearly basis
Papers
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Katholieke Universiteit Leuven1, New Generation University College2, Yale Cancer Center3, Seoul National University Bundang Hospital4, Pontifical Catholic University of Chile5, Yonsei University6, Samsung Medical Center7, Universidad del Desarrollo8, University of Chile9, Harvard University10, Northwestern University11, City of Hope National Medical Center12, University of California, San Francisco13, University of California, Los Angeles14, Merck & Co.15, Hebron University16
TL;DR: This phase 3 randomized clinical trial found that among patients with untreated, advanced G/GEJ cancer, pembrolizumab was noninferior to chemotherapy, with fewer adverse events observed.
Abstract: Importance Safe and effective therapies for untreated, advanced gastric/gastroesophageal junction (G/GEJ) cancer remain an unmet need. Objective To evaluate the antitumor activity of pembrolizumab, pembrolizumab plus chemotherapy, or chemotherapy alone in patients with untreated, advanced G/GEJ cancer with programmed cell death ligand 1 (PD-L1) combined positive score (CPS) of 1 or greater. Design, Setting, and Participants The phase 3 KEYNOTE-062 randomized, controlled, partially blinded interventional trial enrolled 763 patients with untreated, locally advanced/unresectable or metastatic G/GEJ cancer with PD-L1 CPS of 1 or greater from 200 centers in 29 countries between September 18, 2015, and May 26, 2017. Interventions Patients were randomized 1:1:1 to pembrolizumab 200 mg, pembrolizumab plus chemotherapy (cisplatin 80 mg/m2/d on day 1 plus fluorouracil 800 mg/m2/d on days 1 to 5 or capecitabine 1000 mg/m2twice daily), or chemotherapy plus placebo, every 3 weeks. Main Outcomes and Measures Primary end points were overall survival (OS) and progression-free survival (PFS) in patients with PD-L1 CPS of 1 or greater or 10 or greater. Results A total of 763 patients were randomized to pembrolizumab (n = 256), pembrolizumab plus chemotherapy (n = 257), or chemotherapy (n = 250). The median (range) age of all patients in the study cohort was 62 (20-87) years; 554 of 763 (72.6%) were men. At final analysis, after a median (range) follow-up of 29.4 (22.0-41.3) months, pembrolizumab was noninferior to chemotherapy for OS in patients with CPS of 1 or greater (median, 10.6 vs 11.1 months; hazard ratio [HR], 0.91; 99.2% CI, 0.69-1.18). Pembrolizumab monotherapy was not superior to chemotherapy in patients with CPS of 1 or greater. Pembrolizumab prolonged OS vs chemotherapy in patients with CPS of 10 or greater (median, 17.4 vs 10.8 months; HR, 0.69; 95% CI, 0.49-0.97), but this difference was not statistically tested. Pembrolizumab plus chemotherapy was not superior to chemotherapy for OS in patients with CPS of 1 or greater (12.5 vs 11.1 months; HR, 0.85; 95% CI, 0.70-1.03;P = .05) or CPS of 10 or greater (12.3 vs 10.8 months; HR, 0.85; 95% CI, 0.62-1.17;P = .16) or for PFS in patients with CPS of 1 or greater (6.9 vs 6.4 months; HR, 0.84; 95% CI, 0.70-1.02;P = .04). Grade 3 to 5 treatment-related adverse event rates for pembrolizumab, pembrolizumab plus chemotherapy, and chemotherapy were 17%, 73%, and 69%, respectively. Conclusions and Relevance This phase 3 randomized clinical trial found that among patients with untreated, advanced G/GEJ cancer, pembrolizumab was noninferior to chemotherapy, with fewer adverse events observed. Pembrolizumab or pembrolizumab plus chemotherapy was not superior to chemotherapy for the OS and PFS end points tested. Trial Registration ClinicalTrials.gov Identifier:NCT02494583
500 citations
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TL;DR: Findings indicate that PI3K inhibition in HER2-overexpressing breast cancer activates a new compensatory pathway that results in ERK dependency.
Abstract: There is a strong rationale to therapeutically target the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway in breast cancer since it is highly deregulated in this disease and it also mediates resistance to anti-HER2 therapies. However, initial studies with rapalogs, allosteric inhibitors of mTORC1, have resulted in limited clinical efficacy probably due to the release of a negative regulatory feedback loop that triggers AKT and ERK signaling. Since activation of AKT occurs via PI3K, we decided to explore whether PI3K inhibitors prevent the activation of these compensatory pathways. Using HER2-overexpressing breast cancer cells as a model, we observed that PI3K inhibitors abolished AKT activation. However, PI3K inhibition resulted in a compensatory activation of the ERK signaling pathway. This enhanced ERK signaling occurred as a result of activation of HER family receptors as evidenced by induction of HER receptors dimerization and phosphorylation, increased expression of HER3 and binding of adaptor molecules to HER2 and HER3. The activation of ERK was prevented with either MEK inhibitors or anti-HER2 monoclonal antibodies and tyrosine kinase inhibitors. Combined administration of PI3K inhibitors with either HER2 or MEK inhibitors resulted in decreased proliferation, enhanced cell death and superior anti-tumor activity compared with single agent PI3K inhibitors. Our findings indicate that PI3K inhibition in HER2-overexpressing breast cancer activates a new compensatory pathway that results in ERK dependency. Combined anti-MEK or anti-HER2 therapy with PI3K inhibitors may be required in order to achieve optimal efficacy in HER2-overexpressing breast cancer. This approach warrants clinical evaluation.
495 citations
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Memorial Sloan Kettering Cancer Center1, Cornell University2, Hebron University3, University of Texas MD Anderson Cancer Center4, University of California, San Francisco5, University of Wisconsin-Madison6, Harvard University7, University of Chicago8, Mayo Clinic9, University of Washington10, Johns Hopkins University11, Seoul National University Hospital12, Trinity College, Dublin13, University of Arizona14, University of Southern California15, Agios Pharmaceuticals16, University of Manchester17, Fudan University18
TL;DR: Progression-free survival was significantly improved with ivosidenib compared with placebo, and ivOSidenib was well tolerated, and this study shows the clinical benefit of targeting IDH1 mutations in advanced,IDH1-mutant cholangiocarcinoma.
Abstract: Summary Background Isocitrate dehydrogenase 1 (IDH1) mutations occur in approximately 13% of patients with intrahepatic cholangiocarcinoma, a relatively uncommon cancer with a poor clinical outcome. The aim of this international phase 3 study was to assess the efficacy and safety of ivosidenib (AG-120)—a small-molecule targeted inhibitor of mutated IDH1—in patients with previously treated IDH1-mutant cholangiocarcinoma. Methods This multicentre, randomised, double-blind, placebo-controlled, phase 3 study included patients from 49 hospitals in six countries aged at least 18 years with histologically confirmed, advanced, IDH1-mutant cholangiocarcinoma who had progressed on previous therapy, and had up to two previous treatment regimens for advanced disease, an Eastern Cooperative Oncology Group performance status score of 0 or 1, and a measurable lesion as defined by Response Evaluation Criteria in Solid Tumors version 1.1. Patients were randomly assigned (2:1) with a block size of 6 and stratified by number of previous systemic treatment regimens for advanced disease to oral ivosidenib 500 mg or matched placebo once daily in continuous 28-day cycles, by means of an interactive web-based response system. Placebo to ivosidenib crossover was permitted on radiological progression per investigator assessment. The primary endpoint was progression-free survival by independent central review. The intention-to-treat population was used for the primary efficacy analyses. Safety was assessed in all patients who had received at least one dose of ivosidenib or placebo. Enrolment is complete; this study is registered with ClinicalTrials.gov , NCT02989857 . Findings Between Feb 20, 2017, and Jan 31, 2019, 230 patients were assessed for eligibility, and as of the Jan 31, 2019 data cutoff date, 185 patients were randomly assigned to ivosidenib (n=124) or placebo (n=61). Median follow-up for progression-free survival was 6·9 months (IQR 2·8–10·9). Progression-free survival was significantly improved with ivosidenib compared with placebo (median 2·7 months [95% CI 1·6–4·2] vs 1·4 months [1·4–1·6]; hazard ratio 0·37; 95% CI 0·25–0·54; one-sided p Interpretation Progression-free survival was significantly improved with ivosidenib compared with placebo, and ivosidenib was well tolerated. This study shows the clinical benefit of targeting IDH1 mutations in advanced, IDH1-mutant cholangiocarcinoma. Funding Agios Pharmaceuticals.
494 citations
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Imperial College London1, Erasmus University Rotterdam2, SOCAR3, Bayer Corporation4, Paris Descartes University5, University of Freiburg6, University of Edinburgh7, University of London8, Tel Aviv University9, University Health Network10, Montreal Heart Institute11, Alfred Hospital12, Sahlgrenska University Hospital13, Medisch Spectrum Twente14, Hebron University15
TL;DR: Addition of nifedipine GITS to conventional treatment of angina pectoris has no effect on major cardiovascular event-free survival and is safe and reduces the need for coronary angiography and interventions.
488 citations
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TL;DR: Diagnosis and treatment of early stages theoretically represent the most consistent possibility of modifying the outcome of NSCLC in terms of disease-free and overall survival.
482 citations
Authors
Showing all 2723 results
Name | H-index | Papers | Citations |
---|---|---|---|
José Baselga | 156 | 707 | 122498 |
M. I. Martínez | 134 | 1251 | 79885 |
Josep Tabernero | 111 | 803 | 68982 |
Jordi Rello | 103 | 694 | 35994 |
Xavier Montalban | 95 | 762 | 52842 |
James M. Downey | 91 | 381 | 29506 |
Enriqueta Felip | 83 | 622 | 53364 |
Joaquim Bellmunt | 82 | 660 | 41472 |
Joan Montaner | 80 | 489 | 22413 |
Marc Miravitlles | 76 | 651 | 25671 |
David H. Salat | 75 | 241 | 36779 |
Eduard Gratacós | 75 | 531 | 20178 |
Alex Rovira | 74 | 356 | 19586 |
Ramon Bataller | 72 | 283 | 19316 |
Maria Buti | 71 | 493 | 26596 |