Mutated p53 portends improvement in outcomes when bevacizumab is combined with chemotherapy in advanced/recurrent endometrial cancer: An NRG Oncology study
Autor: | Cara Mathews, Xun Clare Zhou, Peter G. Rose, Virginia L. Filiaci, Michael T. McHale, Amanda Jackson, Heather A. Lankes, Debra L. Richardson, Douglas A. Levine, Carol Aghajanian, Angeles Alvarez Secord, Krishnansu S. Tewari, Kimberly K. Leslie, Casey Cosgrove, Katherine M. Moxley, Summer B. Dewdney, Yovanni Casablanca, David G. Mutch, Eric J. Devor, Megan E McDonald, Kristina W. Thiel, Adrianne R. Mallen |
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Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
Oncology medicine.medical_specialty Paclitaxel Bevacizumab medicine.medical_treatment Angiogenesis Inhibitors Gynecologic oncology Article Carboplatin 03 medical and health sciences Clinical Trials Phase II as Topic 0302 clinical medicine Internal medicine Antineoplastic Combined Chemotherapy Protocols medicine Humans Stage (cooking) Neoplasm Staging Randomized Controlled Trials as Topic Sirolimus Chemotherapy business.industry Endometrial cancer Obstetrics and Gynecology Cancer Genes p53 medicine.disease Progression-Free Survival Temsirolimus Endometrial Neoplasms Survival Rate Treatment Outcome 030104 developmental biology Epothilones 030220 oncology & carcinogenesis Mutation Biomarker (medicine) Female Neoplasm Recurrence Local Tumor Suppressor Protein p53 business medicine.drug |
Zdroj: | Gynecol Oncol |
ISSN: | 0090-8258 |
Popis: | 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 . |
Databáze: | OpenAIRE |
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