Mutations in Homologous Recombination Genes and Outcomes in Ovarian Carcinoma Patients in GOG 218: An NRG Oncology/Gynecologic Oncology Group Study.
Mutations in Homologous Recombination Genes and Outcomes in Ovarian Carcinoma Patients in GOG 218: An NRG Oncology/Gynecologic Oncology Group Study.
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DOI：
10.1158/1078-0432.ccr-17-1327
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发表时间：
2018-02-15
期刊：
影响因子：
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通讯作者：
Swisher EM
中科院分区：
文献类型：
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作者：
Norquist BM;Brady MF;Harrell MI;Walsh T;Lee MK;Gulsuner S;Bernards SS;Casadei S;Burger RA;Tewari KS;Backes F;Mannel RS;Glaser G;Bailey C;Rubin S;Soper J;Lankes HA;Ramirez NC;King MC;Birrer MJ;Swisher EM
我们假设，BRCA1和BRCA2以外的同源重组修复（HRR）基因的突变改善了接受铂疗法治疗的卵巢癌（OC）患者的结果，并会影响添加延长贝伐单抗的相对好处。
我们从1,195名妇女中序列的DNA和/或肿瘤是GOG-0218的1,195名女性，这是添加到甲vaciz蛋白的贝伐单抗中的随机III试验中，将其定义为16个基因中的HRR中的Carboplatin和Paclitaxel。用于估计无进展生存率（PFS）和总生存期（OS）的相对危害。
在1,195名OC的女性中，与没有突变的女性相比，在307个中发现了HRR突变（25.7％）。 PFS = 0.01; HR 0.67，95％CI 0.50 - 0.90，OS的P = 0.007）和BRCA1突变（危险比（HR）0.80，95％CI 0.66 - 0.97， PFS的p = 0.02; HR 0.74，95％CI 0.59 - 0.94，OS的P = 0.01），对于BRCA2突变（HR 0.52，95％CI 0.40 - 0.67，P <0.0001） CI 0.25 - 0.53，OS的p <0.0001）。
HRR突变（包括非BRCA基因）在OC中显着延长了PFS，应在临床试验中分层。
We hypothesized that mutations in homologous recombination repair (HRR) genes beyond BRCA1 and BRCA2 improve outcomes for ovarian carcinoma (OC) patients treated with platinum therapy and would impact the relative benefit of adding prolonged bevacizumab. We sequenced DNA from blood and/or neoplasm from 1,195 women enrolled in GOG-0218, a randomized phase III trial in advanced OC of bevacizumab added to carboplatin and paclitaxel. Defects in HRR were defined as damaging mutations in 16 genes. Proportional hazards models were used to estimate relative hazards for progression-free survival (PFS) and overall survival (OS). Of 1,195 women with OC, HRR mutations were identified in 307 (25.7%). Adjusted hazards for progression and death compared to those without mutations were lower for women with non-BRCA HRR mutations (HR 0.73, 95% CI 0.57 – 0.94, p=0.01 for PFS; HR 0.67, 95% CI 0.50 – 0.90, p=0.007 for OS) and BRCA1 mutations (hazard ratio (HR) 0.80, 95% CI 0.66 – 0.97, p=0.02 for PFS; HR 0.74, 95% CI 0.59 – 0.94, p=0.01 for OS) and were lowest for BRCA2 mutations (HR 0.52, 95% CI 0.40 – 0.67, p<0.0001 for PFS; HR 0.36, 95% CI 0.25 – 0.53, p<0.0001 for OS). A test of interaction showed no difference in the effect of bevacizumab on PFS between cases with and without mutations. HRR mutations, including non-BRCA genes, significantly prolong PFS and OS in OC and should be stratified for in clinical trials. The benefit of adding bevacizumab was not significantly modified by mutation status.