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Jason konner

Katherine LaVigne, David M Hyman, Qin C Zhou, Alexia Iasonos, William P Tew, Carol Aghajanian, Vicky Makker, Martee L Hensley, Jason Konner, Rachel N Grisham, Nicholas Cangemi, Krysten Soldan, David R Spriggs, Paul J Sabbatini, Roisin E OʼCearbhaill
OBJECTIVE: Hypersensitivity with repeated exposure to platinum agents is common and can preclude continued treatment, even in patients with disease that remains platinum sensitive. We sought to compare the effects of prophylactic, extended carboplatin infusion versus standard infusion on the rate of carboplatin hypersensitivity reactions (HSRs) in women with recurrent ovarian cancer. METHODS: This was a single-institution, randomized, nonblinded trial comparing a graded, 3-hour extended infusion of carboplatin with a standard 30-minute infusion in patients with recurrent ovarian cancer who were enrolled from January 2011 to April 2015...
May 4, 2018: International Journal of Gynecological Cancer
Kathleen N Moore, Lainie P Martin, David M O'Malley, Ursula A Matulonis, Jason A Konner, Ignace Vergote, Jose F Ponte, Michael J Birrer
Resistance to platinum-based therapy poses a significant clinical challenge for the management of advanced ovarian cancer, a leading cause of cancer mortality among women. Mirvetuximab soravtansine is a novel antibody-drug conjugate that targets folate receptor-α, a validated molecular target for therapeutic intervention in this disease. Here, we examine mirvetuximab soravtansine's mechanism of action and pharmacology, and review its clinical evaluation in ovarian cancer to date. We focus on the favorable tolerability and encouraging signals of efficacy that have emerged, most notably in patients with platinum-resistant disease...
January 2018: Future Oncology
Melissa K Frey, Fanny Dao, Narciso Olvera, Jason A Konner, Maura N Dickler, Douglas A Levine
OBJECTIVE: Bevacizumab, a monoclonal antibody to VEGF, has shown efficacy in ovarian, cervical and endometrial cancer in addition to several other solid tumors. Serious side effects include hypertension, proteinuria, bowel perforation, and thrombosis. We tested the hypothesis that genetic variation in hypertension-associated genes is associated with bevacizumab-induced hypertension (BIH). METHODS: Patients with solid tumors treated with bevacizumab in combination with other therapy were identified from six clinical trials...
December 2017: Gynecologic Oncology
Lainie P Martin, Jason A Konner, Kathleen N Moore, Shelly M Seward, Ursula A Matulonis, Raymond P Perez, Ying Su, Anna Berkenblit, Rodrigo Ruiz-Soto, Michael J Birrer
PURPOSE: To characterize folate receptor alpha (FRα) expression in archival and fresh biopsy tumor samples from relapsed ovarian cancer patients. METHODS: Patients with ovarian tumors amenable to biopsy were eligible to enroll. Eligibility included a minimum requirement of FRα positivity in archival tumor samples (≥25% of cells with ≥2+ staining intensity). Patients received mirvetuximab soravtansine at 6mg/kg once every 3weeks. Core needle biopsies were collected before and after treatment and FRα levels assessed by immunohistochemistry...
November 2017: Gynecologic Oncology
Alejandro Jiménez-Sánchez, Danish Memon, Stephane Pourpe, Harini Veeraraghavan, Yanyun Li, Hebert Alberto Vargas, Michael B Gill, Kay J Park, Oliver Zivanovic, Jason Konner, Jacob Ricca, Dmitriy Zamarin, Tyler Walther, Carol Aghajanian, Jedd D Wolchok, Evis Sala, Taha Merghoub, Alexandra Snyder, Martin L Miller
We present an exceptional case of a patient with high-grade serous ovarian cancer, treated with multiple chemotherapy regimens, who exhibited regression of some metastatic lesions with concomitant progression of other lesions during a treatment-free period. Using immunogenomic approaches, we found that progressing metastases were characterized by immune cell exclusion, whereas regressing and stable metastases were infiltrated by CD8(+) and CD4(+) T cells and exhibited oligoclonal expansion of specific T cell subsets...
August 24, 2017: Cell
Britta Weigelt, Iñaki Comino-Méndez, Ino de Bruijn, Lei Tian, Jane L Meisel, Isaac García-Murillas, Charlotte Fribbens, Ros Cutts, Luciano G Martelotto, Charlotte K Y Ng, Raymond S Lim, Pier Selenica, Salvatore Piscuoglio, Carol Aghajanian, Larry Norton, Rajmohan Murali, David M Hyman, Laetitia Borsu, Maria E Arcila, Jason Konner, Jorge S Reis-Filho, Roger A Greenberg, Mark E Robson, Nicholas C Turner
Purpose: Resistance to platinum-based chemotherapy or PARP inhibition in germline BRCA1 or BRCA2 mutation carriers may occur through somatic reversion mutations or intragenic deletions that restore BRCA1 or BRCA2 function. We assessed whether BRCA1/2 reversion mutations could be identified in circulating cell-free DNA (cfDNA) of patients with ovarian or breast cancer previously treated with platinum and/or PARP inhibitors. Experimental Design: cfDNA from 24 prospectively accrued patients with germline BRCA1 or BRCA2 mutations, including 19 patients with platinum-resistant/refractory ovarian cancer and five patients with platinum and/or PARP inhibitor pretreated metastatic breast cancer, was subjected to massively parallel sequencing targeting all exons of 141 genes and all exons and introns of BRCA1 and BRCA2 Functional studies were performed to assess the impact of the putative BRCA1/2 reversion mutations on BRCA1/2 function...
November 1, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Jacob D Soumerai, Andrew D Zelenetz, Craig H Moskowitz, M Lia Palomba, Paul A Hamlin, Ariela Noy, David J Straus, Alison J Moskowitz, Anas Younes, Matthew J Matasar, Steven M Horwitz, Carol S Portlock, Jason A Konner, Mrinal M Gounder, David M Hyman, Martin H Voss, Matthew G Fury, Devika Gajria, Richard D Carvajal, Alan L Ho, Jan H Beumer, Brian Kiesel, Zhigang Zhang, Alice Chen, Richard F Little, Christine Jarjies, Thu O Dang, Fallon France, Nishant Mishra, John F Gerecitano
Purpose: The PARP inhibitor veliparib enhances the cytotoxicity of alkylating agents. This phase I study evaluated veliparib with the bifunctional alkylator bendamustine (VB) in patients with relapsed/refractory lymphoma, multiple myeloma, and solid malignancies, with a cohort expansion of VB with rituximab (VBR) in patients with B-cell lymphomas. Experimental Design: This dose-escalation study evaluated safety, pharmacokinetics, and preliminary efficacy of veliparib (20-400 mg twice a day, days 1-7 of 28-day cycle) and bendamustine (70 and 90 mg/m2 intravenously, days 1 and 2)...
August 1, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Kathleen N Moore, Lainie P Martin, David M O'Malley, Ursula A Matulonis, Jason A Konner, Raymond P Perez, Todd M Bauer, Rodrigo Ruiz-Soto, Michael J Birrer
Purpose This phase I expansion cohort study evaluated the safety and clinical activity of mirvetuximab soravtansine (IMGN853), an antibody-drug conjugate consisting of a humanized anti-folate receptor alpha (FRα) monoclonal antibody linked to the tubulin-disrupting maytansinoid DM4, in a population of patients with FRα-positive and platinum-resistant ovarian cancer. Patients and Methods Patients with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer received IMGN853 at 6...
April 1, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Catherine A Shu, Malcolm C Pike, Anjali R Jotwani, Tara M Friebel, Robert A Soslow, Douglas A Levine, Katherine L Nathanson, Jason A Konner, Angela G Arnold, Faina Bogomolniy, Fanny Dao, Narciso Olvera, Elizabeth K Bancroft, Deborah J Goldfrank, Zsofia K Stadler, Mark E Robson, Carol L Brown, Mario M Leitao, Nadeem R Abu-Rustum, Carol A Aghajanian, Joanne L Blum, Susan L Neuhausen, Judy E Garber, Mary B Daly, Claudine Isaacs, Rosalind A Eeles, Patricia A Ganz, Richard R Barakat, Kenneth Offit, Susan M Domchek, Timothy R Rebbeck, Noah D Kauff
Importance: The link between BRCA mutations and uterine cancer is unclear. Therefore, although risk-reducing salpingo-oophorectomy (RRSO) is standard treatment among women with BRCA mutations (BRCA+ women), the role of concomitant hysterectomy is controversial. Objective: To determine the risk for uterine cancer and distribution of specific histologic subtypes in BRCA+ women after RRSO without hysterectomy. Design, Setting, and Participants: This multicenter prospective cohort study included 1083 women with a deleterious BRCA1 or BRCA2 mutation identified from January 1, 1995, to December 31, 2011, at 9 academic medical centers in the United States and the United Kingdom who underwent RRSO without a prior or concomitant hysterectomy...
November 1, 2016: JAMA Oncology
Katherine M Bell-McGuinn, Jason A Konner, William P Tew, Martee L Hensley, Alexia Iasonos, Eric Charpentier, Svetlana Mironov, Paul Sabbatini, Carol Aghajanian
OBJECTIVE: The aim of the study was to evaluate the activity and tolerability of iniparib monotherapy in women with BRCA1 or BRCA2-associated advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer. METHODS AND MATERIALS: Eligible patients had advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer, germline BRCA1 or BRCA2 mutation, measurable disease, and at least 1 previous treatment regimen of platinum/taxane chemotherapy. Patients received iniparib 8 mg/kg intravenously on days 1 and 4 weekly, with imaging every 8 weeks...
February 2016: International Journal of Gynecological Cancer
Catherine A Shu, Qin Zhou, Anjali R Jotwani, Alexia Iasonos, Mario M Leitao, Jason A Konner, Carol A Aghajanian
OBJECTIVE: Ovarian clear cell carcinomas (OCCCs) are rare, and uncertainty exists as to the optimal treatment paradigm and validity of the FIGO staging system, especially in early-stage disease. METHODS: We performed a retrospective cohort study of all OCCC patients diagnosed and treated at Memorial Sloan Kettering Cancer Center between January 1996 and December 2013. Progression-free survival (PFS) and overall survival (OS) were calculated by stage and race, and comparisons were made using the log-rank test...
November 2015: Gynecologic Oncology
David M Hyman, Alexandra E Snyder, Richard D Carvajal, John F Gerecitano, Martin H Voss, Alan L Ho, Jason Konner, Jennifer L Winkelmann, Megan A Stasi, Kelsey R Monson, Alexia Iasonos, David R Spriggs, Philip Bialer, Mario E Lacouture, Jerrold B Teitcher, Nora Katabi, Matthew G Fury
PURPOSE: Phosphatidylinositol-3-kinase I (PI3K) inhibition sensitizes a wide range of cancer cell lines to platinum/taxane-based chemotherapy. This phase I study combines buparlisib, a pan-class 1A PI3K inhibitor, with two schedules of carboplatin and paclitaxel for patients with advanced solid tumors (, NCT01297452). METHODS: There were two regimens: Group 1 received carboplatin AUC 5 and paclitaxel 175 mg/m(2), on day 1 of a 21-day cycle with pegfilgrastim support; Group 2 received carboplatin AUC 5 (day 1) and paclitaxel 80 mg/m(2) (days 1, 8, and 15) on a 28-day cycle without growth factor support...
April 2015: Cancer Chemotherapy and Pharmacology
Catherine A Shu, Jason A Konner
No abstract text is available yet for this article.
February 2015: Oncologist
Vaagn Andikyan, Fady Khoury-Collado, Samith Sandadi, William P Tew, Roisin E O'Cearbhaill, Jason A Konner, Yukio Sonoda, Richard R Barakat, Dennis S Chi, Nadeem R Abu-Rustum
OBJECTIVE: It is well documented that recurrence after pelvic exenteration remains high (up to 50%), and patients may require a prolonged period of recuperation following this aggressive surgery. We conducted a retrospective review to evaluate the feasibility of administering adjuvant chemotherapy after pelvic exenteration for gynecologic malignancies. METHODS: We reviewed the medical records of patients with any gynecologic cancer who underwent exenterative surgery between January 2005 and February 2011 at our institution...
June 2013: International Journal of Gynecological Cancer
Paul Sabbatini, Takemasa Tsuji, Luis Ferran, Erika Ritter, Christine Sedrak, Kevin Tuballes, Achim A Jungbluth, Gerd Ritter, Carol Aghajanian, Katherine Bell-McGuinn, Martee L Hensley, Jason Konner, William Tew, David R Spriggs, Eric W Hoffman, Ralph Venhaus, Linda Pan, Andres M Salazar, Catherine Magid Diefenbach, Lloyd J Old, Sacha Gnjatic
PURPOSE: Long peptides are efficiently presented to both CD4(+) and CD8(+) T cells after intracellular processing by antigen-presenting cells. To investigate the safety and in vivo immunogenicity of synthetic overlapping long peptides (OLP) from a human tumor self-antigen, we conducted a phase I clinical trial with OLP from cancer-testis antigen NY-ESO-1 in various adjuvant combinations. EXPERIMENTAL DESIGN: Twenty-eight patients with advanced ovarian cancer in second or third remission were enrolled sequentially in three cohorts and received at least one vaccination...
December 1, 2012: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Rachel Nicole Grisham, Christina Adaniel, David M Hyman, Weining Ma, Alexia Iasonos, Carol Aghajanian, Jason Konner
BACKGROUND: Gemcitabine is active in several gynecologic malignancies including ovarian cancer, cervical cancer, and uterine leiomyosarcoma. It has been used in an off-label setting for the treatment of advanced endometrial cancer, despite lack of published data showing efficacy. We performed a retrospective study to determine the progression-free survival and response rate of endometrial cancer patients treated with gemcitabine at Memorial Sloan-Kettering Cancer Center. METHODS: Eligible patients had histologically confirmed advanced (stage IV or recurrent) endometrial cancer that was treated with single-agent gemcitabine at Memorial Sloan-Kettering Cancer Center between 1999 and 2009...
June 2012: International Journal of Gynecological Cancer
Joyce N Barlin, Fanny Dao, Nadim Bou Zgheib, Sarah E Ferguson, Paul J Sabbatini, Martee L Hensley, Katherine M Bell-McGuinn, Jason Konner, William P Tew, Carol Aghajanian, Dennis S Chi
OBJECTIVE: GOG study 172 demonstrated improved progression-free (PFS) and overall (OS) survival for patients with stage III optimally debulked ovarian and peritoneal carcinoma treated with IV/IP paclitaxel and IP cisplatin compared to standard IV therapy. The inpatient administration, toxicity profile, and limited completion rate have been blamed for the lack of acceptance and widespread use of this regimen. We sought to evaluate the PFS, OS, toxicity, and completion rate of a modified outpatient IP regimen...
June 2012: Gynecologic Oncology
Yevgeniy Balagula, Alyx Rosen, Belinda H Tan, Klaus J Busam, Melissa P Pulitzer, Robert J Motzer, Darren R Feldman, Jason A Konner, Diane Reidy-Lagunes, Patricia L Myskowski, Mario E Lacouture
BACKGROUND: Dermatologic adverse events stemming from anticancer therapies have become an increasingly frequent clinical problem. Inhibitors of mammalian target of rapamycin (mTOR), such as temsirolimus and everolimus, have been associated with a high rate of skin eruptions, but their clinical and histopathologic characteristics have not been explored. METHODS: A retrospective analysis of patients who were referred to the Dermatology Service for diagnosis and management of rash in the setting of therapy with the mTOR inhibitors everolimus and temsirolimus was performed...
October 15, 2012: Cancer
Jason Konner, Rachel N Grisham, Jae Park, Owen A O'Connor, Gillian Cropp, Robert Johnson, Alison L Hannah, Martee L Hensley, Paul Sabbatini, Svetlana Mironov, Svetlana Miranov, Samuel Danishefsky, David Hyman, David R Spriggs, Jakob Dupont, Carol Aghajanian
PURPOSE: To determine the maximum tolerated dose and safety of the epothilone, KOS-862, in patients with advanced solid tumors or lymphoma. PATIENTS AND METHODS: Patients were treated weekly for 3 out of 4 weeks (Schedule A) or 2 out of 3 weeks (Schedule B) with KOS-862 (16-120 mg/m(2)). Pharmacokinetic (PK) sampling was performed during cycles 1 and 2; pharmacodynamic (PD) assessment for microtubule bundle formation (MTBF) was performed after the 1st dose, only at or above 100 mg/m(2)...
December 2012: Investigational New Drugs
Jason A Konner, Diana M Grabon, Scott R Gerst, Alexia Iasonos, Howard Thaler, Sandra D Pezzulli, Paul J Sabbatini, Katherine M Bell-McGuinn, William P Tew, Martee L Hensley, David R Spriggs, Carol A Aghajanian
PURPOSE: Intraperitoneal (IP) cisplatin and intravenous (IV) or IP paclitaxel constitute a standard therapy for optimally debulked ovarian cancer. Bevacizumab prolongs progression-free survival (PFS) when included in first-line IV chemotherapy. In this study, the safety and feasibility of adding bevacizumab to a first-line IP regimen were assessed. PATIENTS AND METHODS: Treatment was as follows: paclitaxel 135 mg/m(2) IV over 3 hours day 1, cisplatin 75 mg/m(2) IP day 2, and paclitaxel 60 mg/m(2) IP day 8...
December 10, 2011: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
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