Long-term overall survival and prognostic score predicting survival: the IMPACT study in precision medicine
Long-term overall survival and prognostic score predicting survival: the IMPACT study in precision medicine
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DOI：
10.1186/s13045-019-0835-1
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发表时间：
2019-12-30
影响因子：
28.5
通讯作者：
Kurzrock, Razelle
中科院分区：
文献类型：
--
作者：
Tsimberidou, Apostolia-Maria;Hong, David S.;Kurzrock, Razelle
背景：2007年，我们启动了IMPACT，这是一项针对参与早期临床试验的患者的精准医学计划。我们评估了相关因素，包括基因组匹配的治疗，与总生存期（OS）。患者和方法：我们进行了分子分析（临床实验室改进修正案）（基因= 1改变和接受治疗（匹配，711;不匹配，596;中位年龄，57岁; 39%的男性）。最常见的肿瘤是胃肠道、妇科、乳腺、黑色素瘤和肺。客观缓解率为：匹配16.4%，不匹配5.4%（p <0.0001）;客观缓解加疾病稳定≥ 6个月的比率为：匹配35.3%，不匹配20.3%（p <0.001）。各自的中位无进展生存期：4.0和2.8个月（p < .0001）; OS，9.3和7.3个月; 3年，15%对7%; 10年，6%对1%（p < .0001）。与OS较短相关的独立因素（多变量分析）是体力状态> 1（p <.001），肝转移（p < .001），乳酸脱氢酶水平>正常上限（p < .001），PI 3 K/AKT/mTOR通路改变（p < .001）和非匹配治疗（p < .001）。预测较短的OS的五个独立因素被用来设计一个预后scores.Conclusions：匹配的靶向治疗是一个独立的因素预测较长的OS.A评分预测个别患者的死亡风险。
Background: In 2007, we initiated IMPACT, a precision medicine program for patients referred for participation in early-phase clinical trials. We assessed the correlation of factors, including genomically matched therapy, with overall survival (OS).Patients and methods: We performed molecular profiling (Clinical Laboratory Improvement Amendments) (genes = 1 alteration and received therapy (matched, 711; unmatched, 596; median age, 57 years; 39% men). Most common tumors were gastrointestinal, gynecologic, breast, melanoma, and lung. Objective response rates were: matched 16.4%, unmatched 5.4% (p < .0001); objective response plus stable disease >= 6 months rates were: matched 35.3% and unmatched 20.3%, (p < .001). Respective median progression-free survival: 4.0 and 2.8 months (p < .0001); OS, 9.3 and 7.3 months; 3-year, 15% versus 7%; 10-year, 6% vs. 1% (p < .0001). Independent factors associated with shorter OS (multivariate analysis) were performance status > 1 (p < .001), liver metastases (p < .001), lactate dehydrogenase levels > upper limit of normal (p < .001), PI3K/AKT/mTOR pathway alterations (p < .001), and non-matched therapy (p < .001). The five independent factors predicting shorter OS were used to design a prognostic score.Conclusions: Matched targeted therapy was an independent factor predicting longer OS. A score to predict an individual patient's risk of death is proposed.