NewYork-Presbyterian/Weill Cornell Research Presented at American Society of Clinical Oncologists Meeting
Leading Cancer Specialists Are Available for Expert Commentary on the Latest Research Findings
Newswise — NEW YORK (June 3, 2011) -- Among those presenting at this year's American Society of Clinical Oncologists meeting are physician-scientists from NewYork-Presbyterian Hospital/Weill Cornell Medical Center. The meeting takes place June 3–7, at McCormick Place, Chicago.
The following are notable research studies:
•Dr. Mark A. RubinA genomics researcher and pathologist at NewYork-Presbyterian Hospital/Weill Cornell Medical Center and professor of pathology and laboratory medicine and the Homer T. Hirst Professor of Oncology in Pathology at Weill Cornell Medical College
Neuroendocrine prostate cancer (NEPC) is an aggressive variant of prostate cancer that can arise de novo or from existing prostate adenocarcinoma (PCA), and is promoted by the use of hormonal therapy. Drs. Mark A. Rubin, Himisha Beltran, David Rickman and other co-investigators sought to better understand the molecular transformation of NEPC and identify new drug targets. They report that there is likely clonal origin of NEPC from PCA. They discovered significant overexpression and amplification of Aurora kinase A (AURKA) and N-myc (MYCN) in NEPC and in a small subset of PCA, and evidence that they cooperate and induce a neuroendocrine phenotype in prostate cells. In vitro and in vivo drug therapy using the Aurora Kinase inhibitor PHA-739358 revealed dramatic and preferential anti-tumor activity against NEPC compared to PCA, suggesting that this is a novel drug target for NEPC.
"Molecular characterization of neuroendocrine prostate cancer (NEPC) and identification of new drug targets." Abstract # 4536. McCormick Place E450a. Saturday, June 4, 2:00 – 6:00 p.m. CT.
•Dr. John P. LeonardA hematologist-oncologist at NewYork-Presbyterian Hospital/Weill Cornell Medical Center and professor of medicine and Richard T. Silver Distinguished Professor of Hematology and Medical Oncology at Weill Cornell Medical College
The recognition of prognostically distinct subtypes of DLBCL by gene expression profiling has, until now, not led to improved outcomes. Conducting targeted studies in prospectively identified, molecularly distinct entities is challenging. PYRAMID and LYM2034 are prospectively identifying and enrolling non-GCB patients. This subtype has inferior outcomes vs. GCB following (R-) CHOP alone (Lenz, NEJM 2008; Fu, JCO 2008). Dr. Leonard and his co-investigators report that the rationale for these studies is provided by data suggesting bortezomib shows benefit specifically in non-GCB DLBCL resulting from inhibition of the critical NF-κB survival pathway, which is activated in the non-GCB subtype. Bortezomib + dose-adjusted EPOCH showed superior response rates and survival in non-GCB vs. GCB relapsed DLBCL (Dunleavy, Blood 2009), and in newly diagnosed DLBCL, bortezomib + R-CHOP showed similar outcomes in GCB and non-GCB patients (Ruan, JCO 2010). PYRAMID is enrolling patients at 55 centers in the U.S.; LYM2034 is enrolling patients at 86 sites in Canada, Australia, and countries in Central and South America, Europe and Asia. Dr. Leonard is a consultant or has an advisory role and has received honoraria and research funding from Millennium Pharmaceuticals, the makers of bortezomib.
"PYRAMID and LYM2034: Targeted randomized phase II studies of bortezomib with or without immunochemotherapy in newly diagnosed nongerminal center B-cell-like (GCB) diffuse large B-cell lymphoma (DLBCL), including rapid prospective non-GCB subtype identification." Abstract # TPS226. McCormick Place Hall A. Monday, June 6, 8:00 a.m. – 12:00 p.m. CT.
•Dr. Rubin NiesvizkyDirector of the Multiple Myeloma Service at the Center of Excellence for Lymphoma and Myeloma at NewYork-Presbyterian Hospital/Weill Cornell Medical Center and associate professor of medicine at Weill Cornell Medical College
The multicenter, Phase IIIb UPFRONT study compares the efficacy and safety of 3 bortezomib (Vc)-based induction regimens, VcD (Vc–dexamethasone), VcTD (Vc–thalidomide–dexamethasone) and VcMP (Vc–melphalan–prednisone), followed by weekly Vc maintenance, in newly diagnosed MM patients ineligible for HDT–SCT. Dr. Niesvizky and his co-investigators report the results of this subgroup analysis, showing that patients <75 years had higher rates of ≥VGPR and lower rates of grade ≥3 adverse events in the UPFRONT study. These results suggest that Vc-containing regimens are active across various patient subgroups including gender, race, co-morbidity status and ISS stage. Dr. Niesvizky is a consultant or has an advisory role and has received research funding from Celgene, Millennium Pharmaceuticals and Onyx Pharmaceuticals.
"Impact of baseline characteristics on efficacy and safety after bortezomib-based induction and maintenance in newly diagnosed multiple myeloma (MM) patients ineligible for transplant in the phase IIIb UPFRONT study." Abstract #8072. McCormick Place Hall A. Monday, June 6, 1:00 p.m. – 5:00 p.m. CT.
•Dr. Linda T. VahdatAn oncologist at NewYork-Presbyterian Hospital/Weill Cornell Medical Center and professor of medicine at Weill Cornell Medical College
Bone-marrow-derived endothelial progenitor cells (EPCs) are critical for metastatic progression. Tetrathiomolybdate (TM), an oral copper-depleting compound, inhibits angiogenesis and maintains tumor dormancy. This study by Dr. Vahdat and her co-investigators explores the effect of TM on EPCs in patients at high risk for breast cancer recurrence. They report that TM is a well-tolerated copper chelator that may contribute to maintaining EPCs below baseline in copper-depleted patients. Further, the rise in EPCs prior to overt relapse in patients with recurrent disease may signify a potential surrogate marker for early relapse. Dr. Vahdat serves as a consultant or has an advisory role for and has received honoraria from Bristol-Myers Squibb and Eisai Pharmaceuticals, and has received research funding from Bristol-Myers Squibb, Celldex, Eisai, ImClone Systems and Novartis.
"The effect of tetrathiomolybdate on endothelial progenitor cells in patients at high risk for breast cancer recurrence." Abstract #1054. McCormick Place Hall A. Monday, June 6, 1:00 p.m. – 5:00 p.m. CT.
•Dr. Nasser AltorkiA cardiothoracic surgeon at NewYork-Presbyterian Hospital/Weill Cornell Medical Center and the David B. Skinner Professor of Thoracic Surgery and professor of cardiothoracic surgery at Weill Cornell Medical College
The Worldwide Esophageal Cancer Collaboration (WECC), a consortium of institutions to pool data on esophageal cancer (EC), reported recommendations regarding the optimal number of lymph nodes removed during esophagectomy. Dr. Nasser Altorki and his co-investigators performed a study to assess how often optimal lymphadenectomy (LAN) was performed in a national EC registry. They report that the SEER database provides insight into practice patterns at U.S. hospitals. In that context, LAN for EC is grossly underperformed when held to the standard of the WECC recommendations. Patients who undergo an optimal LAN have improved survival, likely due to identifying the need for further treatment or to a therapeutic effect of the LAN. Efforts should therefore be made by surgeons to perform a more extensive LAN during esophagectomy to ensure that patients are appropriately staged and treated.
"Quality of lymphadenectomy for esophageal cancer in the United States: An analysis of the SEER database." Abstract # 4068. McCormick Place Hall A. Saturday, June 4, 8:00 a.m. – 12:00 p.m. CT.
The use of neoadjuvant chemotherapy in stage IIIa non-small cell lung cancer (NSCLC) is controversial with trials consistently failing to demonstrate a significant benefit. The ability to identify chemoresponsive tumors should aid clinical trial design and outcome. Cancer-Testis antigens (CTAg), such as MAGE A3, are currently being investigated as immunotherapeutic targets in the adjuvant setting. CTAgs are expressed in over 50 percent of both squamous cell and adenocarcinomas but restricted to testis in normal tissues. Since CTAgs have been proposed as markers of drug-resistant stem-like cells, Dr. Altorki and his co-investigators looked at their expression and association with chemosensitivity. They report that expression of NY-ESO-1 predicts response to neoadjuvant chemotherapy in stage IIIa NSCLC. Expression occurred independent of common mutations but in both adenocarcinoma and squamous cell carcinoma. Given their immunogenicity, immunological mechanisms for these responses are being investigated."NY-ESO-1 as a predictive marker for neoadjuvant chemotherapy in stage IIIa non-small cell lung cancer (NSCLC)." Abstract # 10576. McCormick Place Hall A. Monday, June 6, 8:00 a.m. – 12:00 p.m. CT.
•Dr. Scott T. TagawaA hematologist-oncologist at NewYork-Presbyterian Hospital/Weill Cornell Medical Center and assistant professor of medicine at Weill Cornell Medical College
J591 is a monoclonal antibody which selectively binds the external domain of prostate-specific membrane antigen (PSMA), a protein which is on the surface of prostate cancer cells, but virtually nowhere else in the body. There is no direct effect on PSA expression or secretion. Four trials of radiolabeled-J591 (a small radioactive particle attached to J591) have been presented and/or published. 90Y is a beta-emitter optimal for tumor lesions 28–42 mm; 177Lu is best suited for 1–3 mm lesions. Dr. Tagawa and his co-investigators report: With a decade of experience, RL-J591 has demonstrated efficacy, producing PSA declines which correlate with measurable response and appear to translate into survival benefit. As predicted based on physical properties, 177Lu-J591 appears more effective for lower-volume disease, with objective responses in bulky disease only with 90Y-J591. These results have led to a multicenter study at institutions across the U.S. for men with rising PSA despite surgery and/or radiation and hormonal therapy. Based upon the preliminary data, it is hoped that this targeted form of radiation leads to delays and/or prevention of metastases.
"Radiolabeled anti-prostate-specific membrane antigen (PSMA) monoclonal antibody J591 for metastatic castration-resistant prostate cancer (CRPC)." Publication-only abstract (#e15186).
"Radiolabeled anti-prostate specific membrane antigen (PSMA) monoclonal antibody J591 (177Lu-J591) for non-metastatic castration-resistant prostate cancer (CRPC): A randomized phase II trial." Abstract # TPS193. McCormick Place Hall A, Monday, June 6, 8:00 a.m. – 12:00 p.m. CT.
For more information on American Society of Clinical Oncologists meeting, visit www.asco.org.
NewYork-Presbyterian Hospital/Weill Cornell Medical CenterNewYork-Presbyterian Hospital/Weill Cornell Medical Center, located in New York City, is one of the leading academic medical centers in the world, comprising the teaching hospital NewYork-Presbyterian and Weill Cornell Medical College, the medical school of Cornell University. NewYork-Presbyterian/Weill Cornell provides state-of-the-art inpatient, ambulatory and preventive care in all areas of medicine, and is committed to excellence in patient care, education, research and community service. Weill Cornell physician-scientists have been responsible for many medical advances -- including the development of the Pap test for cervical cancer; the synthesis of penicillin; the first successful embryo-biopsy pregnancy and birth in the U.S.; the first clinical trial for gene therapy for Parkinson's disease; the first indication of bone marrow's critical role in tumor growth; and, most recently, the world's first successful use of deep brain stimulation to treat a minimally conscious brain-injured patient. NewYork-Presbyterian Hospital also comprises NewYork-Presbyterian Hospital/Columbia University Medical Center, NewYork-Presbyterian/Morgan Stanley Children's Hospital, NewYork-Presbyterian Hospital/Westchester Division and NewYork-Presbyterian/The Allen Hospital. NewYork-Presbyterian is the #1 hospital in the New York metropolitan area and is consistently ranked among the best academic medical institutions in the nation, according to U.S.News & World Report. Weill Cornell Medical College is the first U.S. medical college to offer a medical degree overseas and maintains a strong global presence in Austria, Brazil, Haiti, Tanzania, Turkey and Qatar. For more information, visit www.nyp.org and weill.cornell.edu.
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