Morán Teresa, Felip Eudald, Bosch-Barrera Joaquim, de Aguirre Itziar, Ramirez Jose Luis, Mesia Carles, Carcereny Enric, Roa Diana, Sais Elia, García Yolanda, Blanco Remei, Sanchez Silvia, Villacorta Claudia Rosa, Queralt Cristina, Velarde Jose María, Rosell Rafael
Medical Oncology Department, Catalan Institute of Oncology - Badalona, Hospital Universitari Germans Trias i Pujol, Badalona, Universitat Autònoma de Barcelona (UAB), Barcelona, Spain.
Medical Oncology Department, Catalan Institute of Oncology-Girona, Hospital Universitari Doctor Trueta Girona, Girona, Spain.
Oncotarget. 2018 Jun 5;9(43):27074-27086. doi: 10.18632/oncotarget.25478.
Osimertinib is efficacious in lung cancer patients with epidermal growth factor receptor () mutations and acquired resistance (AR) to EGFR tyrosine kinase inhibitors due to -T790M mutation (T790M). We sought to describe T790M changes in serum/plasma during osimertinib therapy and correlate these changes with treatment outcomes.
Serum/plasma from -mutant lung cancer patients with T790M-AR was collected before and during osimertinib treatment. Changes in T790M were evaluated using a peptide-nucleic acid-PCR assay, and correlated with clinical and radiographic response.
Thirteen patients were included. Median time on osimertinib treatment was 10.6 months with a median progression-free survival of 13.6 months. Best response to osimertinib was partial response (PR), stable disease (SD) or progression (PD) in 46.1%, 30.8% and 23.1% of patients, respectively.Most of the patients were paucisymptomatic at baseline. Symptom improvement was reported in 66.6% of responder patients; while symptoms remained stable in 75% of patients with SD, and 66% of patients with PD had clinical deterioration.Three patterns of T790M changes during osimertinib treatment were identified. T790 remained detectable with PD or a short-lasting SD in 15.4% of the patients. T790M disappeared in 69.2% of patients with PR or SD. T790M disappeared, despite clinical and/or radiographic progression in 15.4% of the patients.
Changes of T790M in serum/plasma in -mutant lung cancer patients with T790M-AR might be a useful marker of symptomatic and radiographic outcome to osimertinib. Longer follow-up is needed to establish if subsequent emergence of T790M could be a marker of resistance.
奥希替尼对具有表皮生长因子受体（EGFR）突变且因T790M突变（T790M）而对EGFR酪氨酸激酶抑制剂产生获得性耐药（AR）的肺癌患者有效。我们试图描述奥希替尼治疗期间血清/血浆中T790M的变化，并将这些变化与治疗结果相关联。
收集T790M-AR的EGFR突变肺癌患者在奥希替尼治疗前及治疗期间的血清/血浆。使用肽核酸-PCR检测法评估T790M的变化，并将其与临床和影像学反应相关联。
纳入13例患者。奥希替尼治疗的中位时间为10.6个月，中位无进展生存期为13.6个月。奥希替尼的最佳反应分别为部分缓解（PR）、疾病稳定（SD）或疾病进展（PD），分别占患者的46.1%、30.8%和23.1%。大多数患者在基线时症状较少。66.6%的缓解患者报告症状改善；而75%的SD患者症状保持稳定，66%的PD患者临床症状恶化。确定了奥希替尼治疗期间T790M变化的三种模式。15.4%的患者在疾病进展或短期SD时T790仍可检测到。69.2%的PR或SD患者T790M消失。15.4%的患者尽管有临床和/或影像学进展，但T790M仍消失。
T790M-AR的EGFR突变肺癌患者血清/血浆中T790M的变化可能是奥希替尼症状和影像学结果的有用标志物。需要更长时间的随访来确定T790M随后的出现是否可能是耐药的标志物。
