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
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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