@article{24d5cbfbbabd44479ac753749051241f,
title = "Mutated p53 portends improvement in outcomes when bevacizumab is combined with chemotherapy in advanced/recurrent endometrial cancer: An NRG Oncology study",
abstract = "Background: Successfully combining targeted agents with chemotherapy is an important future goal for cancer therapy. However, an improvement in patient outcomes requires an enhanced understanding of the tumor biomarkers that predict for drug sensitivity. NRG Oncology/Gynecologic Oncology Group (GOG) Study GOG-86P was one of the first attempts to combine targeted agents (bevacizumab or temsirolimus) with chemotherapy in patients with advanced endometrial cancer. Herein we performed exploratory analyses to examine the relationship between mutations in TP53, the most commonly mutated gene in cancer, with outcomes on GOG-86P. Methods: TP53 mutational status was determined and correlated with progression-free survival (PFS) and overall survival (OS) on GOG-86P. Results: Mutations in TP53 were associated with improved PFS and OS for patients that received bevacizumab as compared to temsirolimus (PFS: HR 0.48, 95% CI 0.31, 0.75; OS: HR: 0.61, 95% CI 0.38, 0.98). By contrast, there was no statistically significant difference in PFS or OS between arms for cases with WT TP53. Conclusions: This exploratory study suggests that combining chemotherapy with bevacizumab, but not temsirolimus, may enhance PFS and OS for patients whose tumors harbor mutant p53. These data set the stage for larger clinical studies evaluating the potential of TP53 mutational status as a biomarker to guide choice of treatment for endometrial cancer patients. Clintrials.gov: NCT00977574.",
keywords = "Bevacizumab, Chemotherapy, Endometrial cancer, p53",
author = "Leslie, {Kimberly K.} and Filiaci, {Virginia L.} and Mallen, {Adrianne R.} and Thiel, {Kristina W.} and Devor, {Eric J.} and Katherine Moxley and Debra Richardson and David Mutch and Secord, {Angeles Alvarez} and Tewari, {Krishnansu S.} and McDonald, {Megan E.} and Cara Mathews and Casey Cosgrove and Summer Dewdney and Yovanni Casablanca and Amanda Jackson and Rose, {Peter G.} and Zhou, {Xun Clare} and Michael McHale and Heather Lankes and Levine, {Douglas A.} and Carol Aghajanian",
note = "Funding Information: This work was supported by National Cancer Institute grants to NRG Oncology (U10 CA 180822), NRG Operations (U10 CA180868), and NRG Specimen Bank (U24CA196067). Funding was also received from NIH 2 R01 CA99908-17 to KKL and from the Holden Comprehensive Cancer Center, the University of Iowa (NIH 2 P30 CA086862-16). DAL and CA received funding from American Recovery and Reinvestment Act (ARRA) 3 U10 CA027469-29S1 and a Stand Up to Cancer Dream Team Translational Research Grant, a Program of the Entertainment Industry Foundation (SU2C-AACR-DT0209). The following Gynecologic Oncology Group member institutions participated in the primary treatment studies: University of Oklahoma Health Sciences Center, Washington University School of Medicine, Duke University Medical Center, University of California Irvine Medical Center, University of Iowa Hospitals and Clinics, Women and Infants Hospital, Ohio State University Comprehensive Cancer Center, Rush University Medical Center, Walter Reed National Military Medical Center, University of Cincinnati, Cleveland Clinic Foundation, The Hospital of Central Connecticut, UCSF-Mount Zion, Memorial Sloan Kettering Cancer Center, Mayo Clinic, Cancer Research for the Ozarks NCORP, University of Texas Southwestern Medical Center, Georgia Center for Oncology Research and Education (CORE), Northwestern University, University of North Carolina at Chapel Hill, MD Anderson Cancer Center, University of Wisconsin Hospitals and Clinics, Roswell Park Cancer Institute, University of Colorado Cancer Center – Anschutz Cancer Pavilion, Women's Cancer Center of Nevada, University of Hawaii, Abington Memorial Hospital, University of Mississippi Medical Center, State University of New York Downstate Medical Center, Cooper Hospital University Medical Center, Carolinas Medical Center/Levine Cancer Institute, William Beaumont Hospital, Abramson Cancer Center of the University of Pennsylvania, University of Chicago, Aurora Women's Pavilion of Aurora West Allis Medical Center, Virginia Commonwealth University, Penn State Milton S. Hershey Medical Center, Indiana University Hospital/Melvin and Bren Simon Cancer Center, Stony Brook University Medical Center, University of Massachusetts Memorial Health Care, Fox Chase Cancer Center, University of Virginia, Case Western Reserve University, Yale University, Yale University, University of Texas – Galveston, Michigan Cancer Research Consortium Community Clinical Oncology Program, Delaware/Christiana Care CCOP, University of Minnesota Medical Center-Fairview, University of California at Los Angeles Health System, Fred Hutchinson Cancer Research Center, University of Kentucky, Moffitt Cancer Center and Research Institute, Saint Joseph's Hospital and Medical Center, Scott and White Memorial Hospital, Kalamazoo CCOP, Northern Indiana Cancer Research Consortium, and Iowa-Wide Oncology Research Coalition NCORP. Study concept and design: Dr. Kimberly Leslie, Dr. Virginia Filiaci, Dr. Adrianne Mallen, Dr. Kristina Thiel, Dr. Eric Devor, Dr. Douglas A. Levine and Dr. Carol Aghajanian. Provision of materials or patients: Dr. Katherine Moxley, Dr. Debra Richardson, Dr. David Mutch, Dr. Angeles Alvarez Secord, Dr. Krishnansu Tewari, Dr. Megan E. McDonald, Dr. Cara Mathews, Dr. Casey Cosgrove, Dr. Summer Dewdney, Dr. Yovanni Casablanca, Dr. Amanda Jackson, Dr. Peter Rose, Dr. Xun Clare Zhou, Dr. Michael McHale, Dr. Douglas A. Levine and Dr. Carol Aghajanian, Acquisition of data: Dr. Kimberly Leslie, Dr. Virginia Filiaci, Dr. Kristina Thiel, Dr. Adrianne Mallen, Dr. Eric J. Devor, Dr. Douglas A. Levine and Dr. Carol Aghajanian. Analysis and interpretation of data: Dr. Kimberly Leslie, Dr. Virginia Filiaci, Dr. Adrianne Mallen, Dr. Kristina Thiel, Dr. Eric Devor, Dr. Heather Lankes, Dr. Douglas A. Levine and Dr. Carol Aghajanian. Manuscript writing: Dr. Kimberly Leslie, Dr. Kristina Thiel, Dr. Douglas A. Levine and Dr. Carol Aghajanian. Critical review of the manuscript: Dr. Kimberly Leslie, Dr. Virginia Filiaci, Dr. Adrianne Mallen, Dr. Kristina Thiel, Dr. Eric Devor, Dr. Katherine Moxley, Dr. Debra Richardson, Dr. David Mutch, Dr. Angeles Alvarez Secord, Dr. Krishnansu Tewari, Dr. Megan E. McDonald, Dr. Cara Mathews, Dr. Casey Cosgrove, Dr. Summer Dewdney, Dr. Yovanni Casablanca, Dr. Amanda Jackson, Dr. Peter Rose, Dr. Xun Clare Zhou, Dr. Michael McHale, Dr. Heather Lankes, Dr. Douglas A. Levine and Dr. Carol Aghajanian. Final approval of manuscript: All authors have approved the final manuscript. Funding Information: This work was supported by National Cancer Institute grants to NRG Oncology ( U10 CA 180822 ), NRG Operations ( U10 CA180868 ), and NRG Specimen Bank ( U24CA196067 ). Funding was also received from NIH 2 R01 CA99908-17 to KKL and from the Holden Comprehensive Cancer Center , the University of Iowa ( NIH 2 P30 CA086862-16 ). DAL and CA received funding from American Recovery and Reinvestment Act (ARRA) 3 U10 CA027469-29S1 and a Stand Up to Cancer Dream Team Translational Research Grant, a Program of the Entertainment Industry Foundation ( SU2C-AACR-DT0209 ). Publisher Copyright: {\textcopyright} 2021",
year = "2021",
month = apr,
doi = "10.1016/j.ygyno.2021.01.025",
language = "English (US)",
volume = "161",
pages = "113--121",
journal = "Gynecologic oncology",
issn = "0090-8258",
publisher = "Academic Press Inc.",
number = "1",
}