Department of Obstetrics and Gynecology, University of Iowa, Iowa City, IA 52242, USA; Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA, USA.
NRG Oncology, Clinical Trial Development Division, Biostatistics & Bioinformatics, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA.
Gynecol Oncol. 2021 Apr;161(1):113-121. doi: 10.1016/j.ygyno.2021.01.025. Epub 2021 Feb 2.
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.
TP53 mutational status was determined and correlated with progression-free survival (PFS) and overall survival (OS) on GOG-86P.
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.
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.
成功地将靶向药物与化疗结合是癌症治疗的一个重要未来目标。然而，要提高患者的治疗效果，就需要更深入地了解预测药物敏感性的肿瘤生物标志物。NRG 肿瘤学/妇科肿瘤学组（GOG）的 GOG-86P 研究是首次尝试将靶向药物（贝伐单抗或替西罗莫司）与晚期子宫内膜癌患者的化疗相结合的研究之一。在此，我们进行了探索性分析，以研究癌症中最常见突变基因 TP53 的突变与 GOG-86P 结果之间的关系。
确定 TP53 突变状态，并将其与 GOG-86P 的无进展生存期（PFS）和总生存期（OS）相关联。
与接受替西罗莫司相比，接受贝伐单抗治疗的患者的 TP53 突变与 PFS 和 OS 改善相关（PFS：HR 0.48，95%CI 0.31，0.75；OS：HR：0.61，95%CI 0.38，0.98）。相比之下，WT TP53 病例在两个治疗组之间的 PFS 或 OS 没有统计学上的显著差异。
这项探索性研究表明，将化疗与贝伐单抗联合使用，而不是替西罗莫司，可能会提高肿瘤携带突变 p53 的患者的 PFS 和 OS。这些数据为评估 TP53 突变状态作为生物标志物指导子宫内膜癌患者治疗选择的潜力的更大规模临床试验奠定了基础。Clintrials.gov：NCT00977574。
