Pereira Isabel, Gaspar Cátia, Pina Marta, Azevedo Isabel, Rodrigues Ana
Medical Oncology, Instituto Português de Oncologia do Porto Francisco Gentil, EPE, Porto, PRT.
Cureus. 2020 Dec 17;12(12):e12128. doi: 10.7759/cureus.12128.
Introduction The T790M resistance mutation is present in about one-half of epidermal growth factor receptor (EGFR)-positive advanced non-small cell lung cancer (NSCLC) patients at disease progression. We aimed to assess the prevalence of this mutation in a real-world setting and the clinical impact of repeated biopsies in its detection. Methods This was a single-center retrospective cohort study of patients with EGFR-positive advanced NSCLC diagnosed between 2016 and 2018, who experienced radiographic disease progression during first-line treatment with first- or second-generation EGFR-tyrosine kinase inhibitor (TKI). The frequency of T790M detection and the number of rebiopsies were determined. Results A total of 88 patients were included, with a median age of 65 years (range: 38-84 years). The majority of the participants were females (63 (72%)) and non-smokers (70 (81%)). Upon disease progression, 80 (91%) patients were tested for T790M mutation, and the resistance mutation was detected in 57 (71%) cases (58% in plasma samples and 42% in tissue/cytology samples). In 14 (25%) cases, T790M mutation was only detected after rebiopsy (57% by liquid biopsy), which increased the rate of mutation detection in 17%. Subsequent treatment with third-generation EGFR-TKI was possible in 42 (74%) of T790M-positive cases. Detection of T790M mutation was more likely in patients who were less than 65 years old, with EGFR exon 19 deletions and duration of first-line treatment of more than 12 months (p < 0.05). Conclusions The frequency of T790M mutation in this study was higher than previously reported, suggesting that repeated biopsies after a negative result are beneficial. This allowed a greater percentage of patients to receive sequential osimertinib in our clinical practice.
在疾病进展时，约一半的表皮生长因子受体（EGFR）阳性晚期非小细胞肺癌（NSCLC）患者存在T790M耐药突变。我们旨在评估这种突变在实际临床环境中的发生率，以及重复活检对其检测的临床影响。
这是一项单中心回顾性队列研究，研究对象为2016年至2018年间诊断为EGFR阳性晚期NSCLC且在一线使用第一代或第二代EGFR酪氨酸激酶抑制剂（TKI）治疗期间出现影像学疾病进展的患者。确定T790M检测频率和再次活检次数。
共纳入88例患者，中位年龄65岁（范围：38 - 84岁）。大多数参与者为女性（63例（72%））且不吸烟（70例（81%））。疾病进展时，80例（91%）患者接受了T790M突变检测，其中57例（71%）检测到耐药突变（血浆样本中为58%，组织/细胞学样本中为42%）。在14例（25%）病例中，T790M突变仅在再次活检后检测到（液体活检检测出57%），这使突变检测率提高了17%。42例（74%）T790M阳性病例后续有可能接受第三代EGFR-TKI治疗。年龄小于65岁、存在EGFR外显子19缺失且一线治疗持续时间超过12个月的患者更有可能检测到T790M突变（p < 0.05）。
本研究中T790M突变频率高于先前报道，提示阴性结果后重复活检有益。这使得在我们的临床实践中有更大比例的患者能够序贯使用奥希替尼。
