Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Department of Public Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Cancer Med. 2019 Oct;8(13):5939-5947. doi: 10.1002/cam4.2485. Epub 2019 Aug 21.
Osimertinib yields significant tumor responses and durations of progression-free survival (PFS) in patients with acquired T790M mutations. However, the evidence supporting liquid biopsy-guided treatment is still limited. This study examined the real-world benefits of osimertinib in patients with tissue or plasma T790M mutations.
From January 2016 to June 2018, a total of 183 non-small-cell lung cancer patients were enrolled. The presence of the T790M mutation was assessed by either tissue or plasma. The PFS, overall survival, and tumor response rates of the patients were calculated and compared with those of previous clinical trials.
T790M mutations were detected in 51.5% of the patients, including 64 of 140 (45.7%) who underwent liquid biopsies and 23 of 29 (79.3%) who underwent tumor biopsies. After excluding those in clinical trials, 46 patients received osimertinib, including 33 with positive plasma and 13 with positive tissue results for T790M mutations. The median PFS was 11.3 months (interquartile range: 5.2-NR) in all the T790M-positive patients and 10.1 months (interquartile range: 5.9-NR) in the plasma T790M-positive patients. The overall survival, meanwhile, was not reached, whereas the one-year survival rate was 66.1% in all the patients and 61.4% in those who were plasma T790M-positive. The objective response rate and disease control rate were 37.8% and 91.9% in all the patients and 34.6% and 92.3% in the plasma T790M-positive group, respectively. Using a Cox proportional hazards regression, we determined that male gender was a poor prognostic factor for PFS.
In this retrospective real-world analysis, it was determined that both tissue and plasma T790M mutations can be used to guide treatment with osimertinib. Similar disease control rates and survival durations were observed in comparison to those of phase 3 clinical trials.
奥希替尼可使获得性 T790M 突变的患者获得显著的肿瘤缓解和无进展生存期（PFS）。然而，支持液体活检指导治疗的证据仍然有限。本研究探讨了组织或血浆 T790M 突变指导奥希替尼治疗的真实世界获益。
从 2016 年 1 月至 2018 年 6 月，共纳入 183 例非小细胞肺癌患者。通过组织或血浆评估 T790M 突变的存在。计算患者的 PFS、总生存期和肿瘤缓解率，并与之前的临床试验进行比较。
51.5%的患者检测到 T790M 突变，其中 64 例（45.7%）进行了液体活检，23 例（79.3%）进行了肿瘤活检。排除临床试验患者后，46 例患者接受了奥希替尼治疗，其中 33 例血浆 T790M 阳性，13 例组织 T790M 阳性。所有 T790M 阳性患者的中位 PFS 为 11.3 个月（四分位距：5.2-NR），血浆 T790M 阳性患者的中位 PFS 为 10.1 个月（四分位距：5.9-NR）。总生存期尚未达到，所有患者的 1 年生存率为 66.1%，血浆 T790M 阳性患者的 1 年生存率为 61.4%。所有患者的客观缓解率和疾病控制率分别为 37.8%和 91.9%，血浆 T790M 阳性患者分别为 34.6%和 92.3%。采用 Cox 比例风险回归模型确定男性是 PFS 的不良预后因素。
在本回顾性真实世界分析中，确定组织和血浆 T790M 突变均可用于指导奥希替尼治疗。与 III 期临床试验相比，观察到类似的疾病控制率和生存时间。
