The Experts below are selected from a list of 7545 Experts worldwide ranked by ideXlab platform
Eileen M Oreilly - One of the best experts on this subject based on the ideXlab platform.
-
a randomized multicenter phase ii trial of gemcitabine g cisplatin c veliparib v in patients with Pancreas Adenocarcinoma pdac and a known germline g brca palb2 mutation
Journal of Clinical Oncology, 2020Co-Authors: Eileen M Oreilly, Maeve A Lowery, Marinela Capanu, Joanne F Chou, Jonathan W Lee, Mark M Zalupski, Jennifer Park, Talia Golan, Esther Tahover, Vaibhav SahaiAbstract:639Background: gBRCA 1,2 mutations occur in 5-8% PDAC. Platinum and poly-ADP ribose polymerase inhibitors (PARPi) effective in BRCA-mut cancers. Phase I GC + V high RR 78%; combination may delay re...
-
randomized multicenter phase ii trial of gemcitabine and cisplatin with or without veliparib in patients with Pancreas Adenocarcinoma and a germline brca palb2 mutation
Journal of Clinical Oncology, 2020Co-Authors: Eileen M Oreilly, Maeve A Lowery, Marinela Capanu, Joanne F Chou, Jonathan W Lee, Mark M Zalupski, Jennifer Park, Talia Golan, Esther Tahover, Vaibhav SahaiAbstract:PURPOSEFive percent to 9% of pancreatic ductal Adenocarcinomas (PDACs) develop in patients with a germline BRCA1/2 or PALB2 (gBRCA/PALB2+) mutation. Phase IB data from a trial that used cisplatin, ...
-
pancreatic ductal Adenocarcinoma state of the art 2017 and new therapeutic strategies
Cancer Treatment Reviews, 2017Co-Authors: Marta Chiaravalli, Michele Reni, Eileen M OreillyAbstract:Pancreatic ductal Adenocarcinoma (PDAC) is a fatal malignancy with an overall 5-year survival of 8% for all stages combined. The majority of patients present with stage IV disease at diagnosis and these patients have an overall 5-year survival of 3%. Currently, the standard of care for metastatic Pancreas Adenocarcinoma is combination cytotoxic therapy, namely FOLFIRINOX or gemcitabine plus nab-paclitaxel for good performance status patients. Given the challenges and the rising incidence of PDAC expected to become the second leading cause of cancer-related death by 2030, there is a major unmet need to develop more effective therapies. In this setting, the molecular and genomic characterization of PDAC have underpinned the use of targeted therapies. To date, the results from targeted agent evaluation have been disappointing with some exceptions. Novel promising strategies depend on biomarker identification and patient selection e.g. germline mutations in DNA repair or mismatch repair genes, where the addition of a platinum agent or checkpoint inhibitor can have a positive impact on survival. This article will review the state-of-the-art treatment of metastatic pancreatic cancer with an emphasis on novel promising therapeutic strategies and an overview on emerging biomarkers.
-
phase ib trial of cisplatin c gemcitabine g and veliparib v in patients with known or potential brca or palb2 mutated Pancreas Adenocarcinoma pc
Journal of Clinical Oncology, 2014Co-Authors: Eileen M Oreilly, Maeve A Lowery, Erin E Salomullen, Talia Golan, Michal Segal, Sloane C Smith, Malcolm J Moore, Hedy L Kindler, Amiel Segal, Ellen HollywoodAbstract:4023 Background: 5% to 8% PC have BRCA 1,2 mutations; higher in Ashkenazi Jewish with PC (10-15%). Pre-clinical data demonstrates that DNA-damaging drugs (C) and poly-ADP ribose polymerase inhibito...
-
randomized phase ii study of gemcitabine g cisplatin c with or without veliparib v arms a b and a phase ii single arm study of single agent veliparib arm c in patients with brca or palb2 mutated Pancreas Adenocarcinoma pc
Journal of Clinical Oncology, 2013Co-Authors: Eileen M Oreilly, Maeve A Lowery, Zsofia K Stadler, Erin E Salomullen, Marinela Capanu, Talia Golan, Michal Segal, Amiel Segal, Andrew S Epstein, Laura H TangAbstract:TPS4144 Background: Germline mutations in BRCA1, 2 predispose to PC (Lal, G. Cancer Res, 2000). 5-8% PC have BRCA 1,2 mutations; higher in Ashkenazi Jewish (10-15%). Pre-clinical data demonstrates that platinums and poly-ADP ribose polymerase inhibitors (PARPi) have activity in BRCA-mutated PC models. Early clinical data supporting (Lowery, M. Oncol, 2011). We are evaluating the role of platinum agents and PARPi, veliparib (ABT-888), in BRCA or PALB2-mutated PC. Methods: Arm A, B: Includes non-randomized phase to optimize V dose combined with G, C (Arm A). Subsequently randomized phase II study will evaluate G, C +/- V. Primary endpoint: RECIST 1.1 response rate (RR) G, C, V (Arm A) and G, C (Arm B). Secondary endpoints: Progression-free survival, safety, disease-control rate, overall survival and correlatives involving pre, post biopsies to evaluate mechanisms of sensitivity, resistance to platinums, PARPi. Arm C: Evaluates single-agent V in previously-treated PC. Primary and secondary endpoints similar....
Marinela Capanu - One of the best experts on this subject based on the ideXlab platform.
-
genomic methods identify homologous recombination deficiency in Pancreas Adenocarcinoma and optimize treatment selection
Clinical Cancer Research, 2020Co-Authors: Wungki Park, Marinela Capanu, Jiapeng Chen, Joanne F Chou, Anna M Varghese, Winston WongAbstract:Purpose: Genomic methods can identify homologous recombination deficiency (HRD). Rigorous evaluation of their outcome association to DNA damage response–targeted therapies like platinum in pancreatic ductal Adenocarcinoma (PDAC) is essential in maximizing therapeutic outcome. Experimental Design: We evaluated progression-free survival (PFS) and overall survival (OS) of patients with advanced-stage PDAC, who had both germline- and somatic-targeted gene sequencing. Homologous recombination gene mutations (HRm) were evaluated: BRCA1, BRCA2, PALB2, ATM, BAP1, BARD1, BLM, BRIP1, CHEK2, FAM175A, FANCA, FANCC, NBN, RAD50, RAD51, RAD51C, and RTEL1 HRm status was grouped as: (i) germline versus somatic; (ii) core (BRCAs and PALB2) versus non-core (other HRm); and (iii) monoallelic versus biallelic. Genomic instability was compared using large-scale state transition, signature 3, and tumor mutation burden. Results: Among 262 patients, 50 (19%) had HRD (15% germline and 4% somatic). Both groups were analyzed together due to lack of difference in their genomic instability and outcome. Median [95% confidence interval (CI)] follow-up was 21.9 (1.4–57.0) months. Median OS and PFS were 15.5 (14.6–19) and 7 (6.1–8.1) months, respectively. Patients with HRD had improved PFS compared with no HRD when treated with first-line (1L) platinum [HR, 0.44 (95% CI: 0.29–0.67); P Conclusions: Pathogenic HRm identifies HRD in patients with PDAC with the best outcome when treated with 1L-platinum. Biallelic HRm and core HRm further enriched benefit from 1L-platinum from HRD.
-
a randomized multicenter phase ii trial of gemcitabine g cisplatin c veliparib v in patients with Pancreas Adenocarcinoma pdac and a known germline g brca palb2 mutation
Journal of Clinical Oncology, 2020Co-Authors: Eileen M Oreilly, Maeve A Lowery, Marinela Capanu, Joanne F Chou, Jonathan W Lee, Mark M Zalupski, Jennifer Park, Talia Golan, Esther Tahover, Vaibhav SahaiAbstract:639Background: gBRCA 1,2 mutations occur in 5-8% PDAC. Platinum and poly-ADP ribose polymerase inhibitors (PARPi) effective in BRCA-mut cancers. Phase I GC + V high RR 78%; combination may delay re...
-
randomized multicenter phase ii trial of gemcitabine and cisplatin with or without veliparib in patients with Pancreas Adenocarcinoma and a germline brca palb2 mutation
Journal of Clinical Oncology, 2020Co-Authors: Eileen M Oreilly, Maeve A Lowery, Marinela Capanu, Joanne F Chou, Jonathan W Lee, Mark M Zalupski, Jennifer Park, Talia Golan, Esther Tahover, Vaibhav SahaiAbstract:PURPOSEFive percent to 9% of pancreatic ductal Adenocarcinomas (PDACs) develop in patients with a germline BRCA1/2 or PALB2 (gBRCA/PALB2+) mutation. Phase IB data from a trial that used cisplatin, ...
-
a single arm nonrandomized phase ii trial of neoadjuvant gemcitabine and oxaliplatin in patients with resectable Pancreas Adenocarcinoma
Annals of Surgery, 2014Co-Authors: Eileen M Oʼreilly, Anna Perelshteyn, William R Jarnagin, Mark A Schattner, Hans Gerdes, Marinela Capanu, Laura H Tang, Joseph Lavalle, Corinne B Winston, Ronald P DematteoAbstract:Background:The role for neoadjuvant systemic therapy in resectable Pancreas Adenocarcinoma remains undefined.Objective:We evaluated the efficacy of gemcitabine and oxaliplatin administered as preoperative therapy in patients with resectable Pancreas Adenocarcinoma.Methods:Eligible patients were scre
-
randomized phase ii study of gemcitabine g cisplatin c with or without veliparib v arms a b and a phase ii single arm study of single agent veliparib arm c in patients with brca or palb2 mutated Pancreas Adenocarcinoma pc
Journal of Clinical Oncology, 2013Co-Authors: Eileen M Oreilly, Maeve A Lowery, Zsofia K Stadler, Erin E Salomullen, Marinela Capanu, Talia Golan, Michal Segal, Amiel Segal, Andrew S Epstein, Laura H TangAbstract:TPS4144 Background: Germline mutations in BRCA1, 2 predispose to PC (Lal, G. Cancer Res, 2000). 5-8% PC have BRCA 1,2 mutations; higher in Ashkenazi Jewish (10-15%). Pre-clinical data demonstrates that platinums and poly-ADP ribose polymerase inhibitors (PARPi) have activity in BRCA-mutated PC models. Early clinical data supporting (Lowery, M. Oncol, 2011). We are evaluating the role of platinum agents and PARPi, veliparib (ABT-888), in BRCA or PALB2-mutated PC. Methods: Arm A, B: Includes non-randomized phase to optimize V dose combined with G, C (Arm A). Subsequently randomized phase II study will evaluate G, C +/- V. Primary endpoint: RECIST 1.1 response rate (RR) G, C, V (Arm A) and G, C (Arm B). Secondary endpoints: Progression-free survival, safety, disease-control rate, overall survival and correlatives involving pre, post biopsies to evaluate mechanisms of sensitivity, resistance to platinums, PARPi. Arm C: Evaluates single-agent V in previously-treated PC. Primary and secondary endpoints similar....
Maeve A Lowery - One of the best experts on this subject based on the ideXlab platform.
-
a randomized multicenter phase ii trial of gemcitabine g cisplatin c veliparib v in patients with Pancreas Adenocarcinoma pdac and a known germline g brca palb2 mutation
Journal of Clinical Oncology, 2020Co-Authors: Eileen M Oreilly, Maeve A Lowery, Marinela Capanu, Joanne F Chou, Jonathan W Lee, Mark M Zalupski, Jennifer Park, Talia Golan, Esther Tahover, Vaibhav SahaiAbstract:639Background: gBRCA 1,2 mutations occur in 5-8% PDAC. Platinum and poly-ADP ribose polymerase inhibitors (PARPi) effective in BRCA-mut cancers. Phase I GC + V high RR 78%; combination may delay re...
-
randomized multicenter phase ii trial of gemcitabine and cisplatin with or without veliparib in patients with Pancreas Adenocarcinoma and a germline brca palb2 mutation
Journal of Clinical Oncology, 2020Co-Authors: Eileen M Oreilly, Maeve A Lowery, Marinela Capanu, Joanne F Chou, Jonathan W Lee, Mark M Zalupski, Jennifer Park, Talia Golan, Esther Tahover, Vaibhav SahaiAbstract:PURPOSEFive percent to 9% of pancreatic ductal Adenocarcinomas (PDACs) develop in patients with a germline BRCA1/2 or PALB2 (gBRCA/PALB2+) mutation. Phase IB data from a trial that used cisplatin, ...
-
phase ib trial of cisplatin c gemcitabine g and veliparib v in patients with known or potential brca or palb2 mutated Pancreas Adenocarcinoma pc
Journal of Clinical Oncology, 2014Co-Authors: Eileen M Oreilly, Maeve A Lowery, Erin E Salomullen, Talia Golan, Michal Segal, Sloane C Smith, Malcolm J Moore, Hedy L Kindler, Amiel Segal, Ellen HollywoodAbstract:4023 Background: 5% to 8% PC have BRCA 1,2 mutations; higher in Ashkenazi Jewish with PC (10-15%). Pre-clinical data demonstrates that DNA-damaging drugs (C) and poly-ADP ribose polymerase inhibito...
-
randomized phase ii study of gemcitabine g cisplatin c with or without veliparib v arms a b and a phase ii single arm study of single agent veliparib arm c in patients with brca or palb2 mutated Pancreas Adenocarcinoma pc
Journal of Clinical Oncology, 2013Co-Authors: Eileen M Oreilly, Maeve A Lowery, Zsofia K Stadler, Erin E Salomullen, Marinela Capanu, Talia Golan, Michal Segal, Amiel Segal, Andrew S Epstein, Laura H TangAbstract:TPS4144 Background: Germline mutations in BRCA1, 2 predispose to PC (Lal, G. Cancer Res, 2000). 5-8% PC have BRCA 1,2 mutations; higher in Ashkenazi Jewish (10-15%). Pre-clinical data demonstrates that platinums and poly-ADP ribose polymerase inhibitors (PARPi) have activity in BRCA-mutated PC models. Early clinical data supporting (Lowery, M. Oncol, 2011). We are evaluating the role of platinum agents and PARPi, veliparib (ABT-888), in BRCA or PALB2-mutated PC. Methods: Arm A, B: Includes non-randomized phase to optimize V dose combined with G, C (Arm A). Subsequently randomized phase II study will evaluate G, C +/- V. Primary endpoint: RECIST 1.1 response rate (RR) G, C, V (Arm A) and G, C (Arm B). Secondary endpoints: Progression-free survival, safety, disease-control rate, overall survival and correlatives involving pre, post biopsies to evaluate mechanisms of sensitivity, resistance to platinums, PARPi. Arm C: Evaluates single-agent V in previously-treated PC. Primary and secondary endpoints similar....
-
an emerging entity pancreatic Adenocarcinoma associated with a known brca mutation clinical descriptors treatment implications and future directions
Oncologist, 2011Co-Authors: Maeve A Lowery, Mark E Robson, David P Kelsen, Zsofia K Stadler, Kenneth H Yu, Yelena Y Janjigian, Emmy Ludwig, David R Dadamo, Erin E Salomullen, Peter J AllenAbstract:Background. BRCA1 and BRCA2 germline mutations are associated with an elevated risk for Pancreas Adenocarcinoma (PAC). Other BRCA-associated cancers have been shown to have greater sensitivity to platinum and poly(ADP-ribose) polymerase (PARP) inhibitors with better clinical outcomes than in sporadic cases; however, outcomes in BRCA-associated PAC have not been reported. Methods. Patients with a known BRCA1 or BRCA2 mutationandadiagnosisofPACwereidentifiedfromtheGastrointestinal Oncology Service, Familial Pancreas Cancer Registry, and Clinical Genetics Service at Memorial SloanKettering Cancer Center. Results. Fifteen patients, five male, with a BRCA1 (n 4) or BRCA2 (n 11) mutation and PAC and one patient with a BRCA1 mutation and acinar cell carcinoma of the Pancreas were identified. Seven female patients (70%) had a prior history of breast cancer. Four patients received a PARP inhibitor alone or in combination with chemotherapy; three demonstrated an initial radiographic partial response by Response Evaluation Criteria in Solid Tumors whereas one patient had stable disease for 6 months. Six patients received platinumbased chemotherapy first line for metastatic disease; five of those patients had a radiographic partial response. Conclusion. BRCA mutation–associated PAC represents an underidentified, but clinically important, subgroup of patients. This is of particular relevance given the ongoing development of therapeutic agents targeting DNA repair, which may potentially offer a significant benefit to a genetically selected population. We anticipate that further study and understanding of the clinical and biologic features of BRCA-mutant PAC will aid in the identification of tissue biomarkers indicating defective tumor DNA repair pathways in sporadic PAC. The Oncologist 2011;16:000–000
Laura H Tang - One of the best experts on this subject based on the ideXlab platform.
-
a single arm nonrandomized phase ii trial of neoadjuvant gemcitabine and oxaliplatin in patients with resectable Pancreas Adenocarcinoma
Annals of Surgery, 2014Co-Authors: Eileen M Oʼreilly, Anna Perelshteyn, William R Jarnagin, Mark A Schattner, Hans Gerdes, Marinela Capanu, Laura H Tang, Joseph Lavalle, Corinne B Winston, Ronald P DematteoAbstract:Background:The role for neoadjuvant systemic therapy in resectable Pancreas Adenocarcinoma remains undefined.Objective:We evaluated the efficacy of gemcitabine and oxaliplatin administered as preoperative therapy in patients with resectable Pancreas Adenocarcinoma.Methods:Eligible patients were scre
-
failure patterns in resected Pancreas Adenocarcinoma lack of predicted benefit to smad4 expression
Annals of Surgery, 2013Co-Authors: Jordan M Winter, Laura H Tang, Ronald P Dematteo, David S Klimstra, Weiguo Liu, Irena Linkov, Murray F Brennan, Michael I Dʼangelica, Yuman Fong, William R JarnaginAbstract:Objective:To determine whether SMAD4 expression is associated with recurrence pattern after resection for pancreatic ductal Adenocarcinoma (PDA).Background:SMAD4 expression status has been reported to be associated with patterns of failure in PDA, but studies have not examined recurrence patterns af
-
randomized phase ii study of gemcitabine g cisplatin c with or without veliparib v arms a b and a phase ii single arm study of single agent veliparib arm c in patients with brca or palb2 mutated Pancreas Adenocarcinoma pc
Journal of Clinical Oncology, 2013Co-Authors: Eileen M Oreilly, Maeve A Lowery, Zsofia K Stadler, Erin E Salomullen, Marinela Capanu, Talia Golan, Michal Segal, Amiel Segal, Andrew S Epstein, Laura H TangAbstract:TPS4144 Background: Germline mutations in BRCA1, 2 predispose to PC (Lal, G. Cancer Res, 2000). 5-8% PC have BRCA 1,2 mutations; higher in Ashkenazi Jewish (10-15%). Pre-clinical data demonstrates that platinums and poly-ADP ribose polymerase inhibitors (PARPi) have activity in BRCA-mutated PC models. Early clinical data supporting (Lowery, M. Oncol, 2011). We are evaluating the role of platinum agents and PARPi, veliparib (ABT-888), in BRCA or PALB2-mutated PC. Methods: Arm A, B: Includes non-randomized phase to optimize V dose combined with G, C (Arm A). Subsequently randomized phase II study will evaluate G, C +/- V. Primary endpoint: RECIST 1.1 response rate (RR) G, C, V (Arm A) and G, C (Arm B). Secondary endpoints: Progression-free survival, safety, disease-control rate, overall survival and correlatives involving pre, post biopsies to evaluate mechanisms of sensitivity, resistance to platinums, PARPi. Arm C: Evaluates single-agent V in previously-treated PC. Primary and secondary endpoints similar....
Talia Golan - One of the best experts on this subject based on the ideXlab platform.
-
a randomized multicenter phase ii trial of gemcitabine g cisplatin c veliparib v in patients with Pancreas Adenocarcinoma pdac and a known germline g brca palb2 mutation
Journal of Clinical Oncology, 2020Co-Authors: Eileen M Oreilly, Maeve A Lowery, Marinela Capanu, Joanne F Chou, Jonathan W Lee, Mark M Zalupski, Jennifer Park, Talia Golan, Esther Tahover, Vaibhav SahaiAbstract:639Background: gBRCA 1,2 mutations occur in 5-8% PDAC. Platinum and poly-ADP ribose polymerase inhibitors (PARPi) effective in BRCA-mut cancers. Phase I GC + V high RR 78%; combination may delay re...
-
randomized multicenter phase ii trial of gemcitabine and cisplatin with or without veliparib in patients with Pancreas Adenocarcinoma and a germline brca palb2 mutation
Journal of Clinical Oncology, 2020Co-Authors: Eileen M Oreilly, Maeve A Lowery, Marinela Capanu, Joanne F Chou, Jonathan W Lee, Mark M Zalupski, Jennifer Park, Talia Golan, Esther Tahover, Vaibhav SahaiAbstract:PURPOSEFive percent to 9% of pancreatic ductal Adenocarcinomas (PDACs) develop in patients with a germline BRCA1/2 or PALB2 (gBRCA/PALB2+) mutation. Phase IB data from a trial that used cisplatin, ...
-
phase ib trial of cisplatin c gemcitabine g and veliparib v in patients with known or potential brca or palb2 mutated Pancreas Adenocarcinoma pc
Journal of Clinical Oncology, 2014Co-Authors: Eileen M Oreilly, Maeve A Lowery, Erin E Salomullen, Talia Golan, Michal Segal, Sloane C Smith, Malcolm J Moore, Hedy L Kindler, Amiel Segal, Ellen HollywoodAbstract:4023 Background: 5% to 8% PC have BRCA 1,2 mutations; higher in Ashkenazi Jewish with PC (10-15%). Pre-clinical data demonstrates that DNA-damaging drugs (C) and poly-ADP ribose polymerase inhibito...
-
randomized phase ii study of gemcitabine g cisplatin c with or without veliparib v arms a b and a phase ii single arm study of single agent veliparib arm c in patients with brca or palb2 mutated Pancreas Adenocarcinoma pc
Journal of Clinical Oncology, 2013Co-Authors: Eileen M Oreilly, Maeve A Lowery, Zsofia K Stadler, Erin E Salomullen, Marinela Capanu, Talia Golan, Michal Segal, Amiel Segal, Andrew S Epstein, Laura H TangAbstract:TPS4144 Background: Germline mutations in BRCA1, 2 predispose to PC (Lal, G. Cancer Res, 2000). 5-8% PC have BRCA 1,2 mutations; higher in Ashkenazi Jewish (10-15%). Pre-clinical data demonstrates that platinums and poly-ADP ribose polymerase inhibitors (PARPi) have activity in BRCA-mutated PC models. Early clinical data supporting (Lowery, M. Oncol, 2011). We are evaluating the role of platinum agents and PARPi, veliparib (ABT-888), in BRCA or PALB2-mutated PC. Methods: Arm A, B: Includes non-randomized phase to optimize V dose combined with G, C (Arm A). Subsequently randomized phase II study will evaluate G, C +/- V. Primary endpoint: RECIST 1.1 response rate (RR) G, C, V (Arm A) and G, C (Arm B). Secondary endpoints: Progression-free survival, safety, disease-control rate, overall survival and correlatives involving pre, post biopsies to evaluate mechanisms of sensitivity, resistance to platinums, PARPi. Arm C: Evaluates single-agent V in previously-treated PC. Primary and secondary endpoints similar....
