Jessica Gillen1, Austin Miller2, Katherine M Bell-McGuinn3, Russell J Schilder4, Joan L Walker5, Cara A Mathews6, Linda R Duska7, Saketh R Guntupalli8, Roisin O'Cearbhaill9, John Hays10, Andrea R Hagemann11, Heidi J Gray12, Sarah W Gordon13, Deborah K Armstrong14, Alice Chen15, Paula M Fracasso16, Carol Aghajanian17, Kathleen N Moore18. 1. Stephenson Cancer Center at the University of Oklahoma, Oklahoma City, OK, United States of America. Electronic address: Jessica-Gillen@ouhsc.edu. 2. NRG Oncology SDMC, CTD Division, Roswell Park Cancer Institute, Buffalo, NY, United States of America. Electronic address: millerA@nrgoncology.org. 3. Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY, United States of America. Electronic address: Katherine.bellmcguinn@abbvie.com. 4. Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, United States of America. Electronic address: russell.schilder@jefferson.edu. 5. Stephenson Cancer Center at the University of Oklahoma, Oklahoma City, OK, United States of America. Electronic address: joan-walker@ouhsc.edu. 6. Women and Infants Hospital of Rhode Island, Providence, RI, United States of America. Electronic address: cmathews@wihri.org. 7. University of Virginia School of Medicine, Charlottesville, VA, United States of America. Electronic address: lduska@virginia.edu. 8. University of Colorado, Denver, CO, United States of America. Electronic address: saketh.guntupalli@UCDENVER.edu. 9. Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY, United States of America. Electronic address: ocearbhr@mskcc.org. 10. The Ohio State University, Columbus, OH, United States of America. Electronic address: john.hays@osumc.edu. 11. Washington University, St. Louis, MO, United States of America. Electronic address: hagemanna@wustl.edu. 12. University of Washington, Seattle, WA, United States of America. Electronic address: hgray@u.washington.edu. 13. Virginia Commonwealth University, Richmond, VA, United States of America. Electronic address: sarah.gordon@vcuhealth.org. 14. Johns Hopkins University, Baltimore, MD, United States of America. Electronic address: armstde@jhmi.edu. 15. Division of Cancer Treatment and Diagnosis, NCI, NIH, Bethesda, MD, United States of America. Electronic address: chenali@mail.nih.gov. 16. University of Virginia School of Medicine, Charlottesville, VA, United States of America. Electronic address: fracasso@virginia.edu. 17. Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY, United States of America. Electronic address: aghajanc@mskcc.org. 18. Stephenson Cancer Center at the University of Oklahoma, Oklahoma City, OK, United States of America. Electronic address: Kathleen-Moore@ouhsc.edu.
Abstract
OBJECTIVE: To evaluate how women with epithelial ovarian cancer (EOC), dichotomized by BRCA status, tolerate intravenous (IV) or intraperitoneal (IP) chemotherapy given with veliparib and bevacizumab (bev) on a GOG phase I study (GOG 9923, NCT00989651). METHODS: This is an unplanned, post hoc analysis of an IRB approved, multi-institutional, prospective study (GOG 9923). Clinical characteristics and toxicity data based on BRCA status were evaluated and descriptive statistics were used to summarize baseline patient characteristics and toxicities. The Kaplan Meier method was used to generate survival estimates. RESULTS: Four hundred twenty-four patients were evaluable. Patients were treated with IV carboplatin, paclitaxel, and bev every 21 days (regimen 1), weekly IV paclitaxel with carboplatin and bev (regimen 2) or IV paclitaxel and bev with IP cisplatin (regimen 3). Bev was continued as maintenance in all arms. Within each of these regimens, veliparib was given either twice daily for the entirety of each cycle (continuous) or on days -2 to 5 (intermittent). Ten percent of patients treated on regimen 1, 12% on regimen 2, and 19.8% on regimen 3 had BRCA-associated tumors. Patients with BRCA-associated tumors, when compared to wild type, experienced similar rates of anemia, febrile neutropenia (, abdominal pain, colonic perforation, nausea, vomiting, and peripheral sensory neuropathy. Median progression free survival (PFS) was not significantly different between BRCA-associated and wild type cancers (HR 0.96, CI 0.65-1.42), though this study's primary aim was not to evaluate outcomes. CONCLUSIONS: Germline BRCA mutations positively affect chemosensitivity in EOC, but whether differences in toxicities among BRCA-associated and BRCA wild type tumors existed was previously not reported. In this population with newly diagnosed ovarian cancer no differences in reported toxicity between the two groups was observed.
OBJECTIVE: To evaluate how women with epithelial ovarian cancer (EOC), dichotomized by BRCA status, tolerate intravenous (IV) or intraperitoneal (IP) chemotherapy given with veliparib and bevacizumab (bev) on a GOG phase I study (GOG 9923, NCT00989651). METHODS: This is an unplanned, post hoc analysis of an IRB approved, multi-institutional, prospective study (GOG 9923). Clinical characteristics and toxicity data based on BRCA status were evaluated and descriptive statistics were used to summarize baseline patient characteristics and toxicities. The Kaplan Meier method was used to generate survival estimates. RESULTS: Four hundred twenty-four patients were evaluable. Patients were treated with IV carboplatin, paclitaxel, and bev every 21 days (regimen 1), weekly IV paclitaxel with carboplatin and bev (regimen 2) or IV paclitaxel and bev with IP cisplatin (regimen 3). Bev was continued as maintenance in all arms. Within each of these regimens, veliparib was given either twice daily for the entirety of each cycle (continuous) or on days -2 to 5 (intermittent). Ten percent of patients treated on regimen 1, 12% on regimen 2, and 19.8% on regimen 3 had BRCA-associated tumors. Patients with BRCA-associated tumors, when compared to wild type, experienced similar rates of anemia, febrile neutropenia (, abdominal pain, colonic perforation, nausea, vomiting, and peripheral sensory neuropathy. Median progression free survival (PFS) was not significantly different between BRCA-associated and wild type cancers (HR 0.96, CI 0.65-1.42), though this study's primary aim was not to evaluate outcomes. CONCLUSIONS: Germline BRCA mutations positively affect chemosensitivity in EOC, but whether differences in toxicities among BRCA-associated and BRCA wild type tumors existed was previously not reported. In this population with newly diagnosed ovarian cancer no differences in reported toxicity between the two groups was observed.
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