Department of Respiratory Medicine, Anhui Provincial Cancer Hospital, The First Affiliated Hospital of USTC West District, Hefei, China.
Graduate School, Bengbu Medical College, Bengbu, China.
Asia Pac J Clin Oncol. 2023 Dec;19(6):715-722. doi: 10.1111/ajco.13935. Epub 2023 Feb 9.
Osimertinib could effectively target epidermal growth factor receptor (EGFR) T790M resistance mutations in non-small cell lung cancer (NSCLC), indicating that rebiopsy may be particularly important. However, the clinical benefit of repeat rebiopsy in T790M-negative patients with NSCLC detected by the first rebiopsy is still unclear, and data on the efficacy and safety of osimertinib in patients with NSCLC who are T790M-positive patients on a repeat rebiopsy remain rare.
We retrospectively collected the clinical data of advanced NSCLC patients with common EGFR mutation who were treated with 1/2-generation (1/2G) EGFR-tyrosine kinase inhibitors (TKIs) in first-line therapy in our center from January 2018 to December 2020. The detection rate of T790M by first and repeat rebiopsy was recorded, and we also analyzed the efficacy and safety of osimertinib for T790M-positive patients.
Among 190 common EGFR-mutant patients who received 1/2G EGFR-TKIs with advanced NSCLC in the first-line treatment, 141 patients developed progressive disease. In total, 110 of 141 accepted the first rebiopsy, with a T790M prevalence of 50.9% (56/110). In total, 43 T790M-positive patients who received osimertinib were included in first rebiopsy group. Of 54 T790M-negative patients detected by the first rebiopsy, 28 underwent repeated rebiopsy in subsequent clinical treatment, and 10 (35.7%) T790M-positive cases were confirmed. In total, eight T790M-positive patients treated with osimertinib were included in repeat rebiopsy group. Overall, 66 (60%) of 110 patients acquired a T790M mutation. In patients with the T790M mutation discovered by the first and repeat rebiopsy, osimertinib resulted in median progression-free survival of 7 (95% confidence interval [CI]: 5.3-8.7) and 6 (95% CI: 4.7-7.3) months, respectively (p = .656). The median overall survival since osimertinib initiation for T790M-positive patients at first rebiopsy was 20 (95% CI: 15.1-24.9) months and 19 (95% CI: 16.9-21.1) months, for those at repeated rebiopsy (p = .888). Adverse events of grade 3 or higher were similar in the two groups (25.6% vs. 12.5%, p = .616). There was no treatment-related death in the two groups.
Repeat rebiopsy can increase the T790M mutation positivity rate. Osimertinib showed similar efficacy and safety in T790M-positive patients whether detected by the first or repeat rebiopsy.
奥希替尼可有效靶向非小细胞肺癌（NSCLC）中的表皮生长因子受体（EGFR）T790M 耐药突变，这表明再次活检可能尤为重要。然而，首次活检检测到 T790M 阴性的 NSCLC 患者重复活检的临床获益仍不清楚，且关于在重复活检中 T790M 阳性的 NSCLC 患者中奥希替尼疗效和安全性的数据仍很少。
我们回顾性收集了 2018 年 1 月至 2020 年 12 月在我院接受一线治疗的常见 EGFR 突变的晚期 NSCLC 患者的临床数据。记录了首次和重复活检中 T790M 的检出率，我们还分析了奥希替尼对 T790M 阳性患者的疗效和安全性。
在 190 名接受一线治疗的常见 EGFR 突变的晚期 NSCLC 患者中，141 名患者发生疾病进展。共有 141 名患者接受了 110 次首次活检，T790M 阳性率为 50.9%（56/110）。在首次活检组中，共有 43 名 T790M 阳性患者接受了奥希替尼治疗。在首次活检中检测到 T790M 阴性的 54 名患者中，28 名在后续临床治疗中接受了重复活检，其中 10 例（35.7%）证实 T790M 阳性。在重复活检组中，共纳入 8 名接受奥希替尼治疗的 T790M 阳性患者。总体而言，110 名患者中有 66 名（60%）检出 T790M 突变。在首次和重复活检发现 T790M 突变的患者中，奥希替尼的中位无进展生存期分别为 7 个月（95%CI：5.3-8.7）和 6 个月（95%CI：4.7-7.3）（p=0.656）。首次重复活检 T790M 阳性患者的奥希替尼起始后中位总生存期为 20 个月（95%CI：15.1-24.9），重复重复活检 T790M 阳性患者为 19 个月（95%CI：16.9-21.1）（p=0.888）。两组中 3 级或以上不良事件发生率相似（25.6%比 12.5%，p=0.616）。两组均无治疗相关死亡。
重复活检可提高 T790M 突变阳性率。无论首次活检还是重复活检检测到 T790M 阳性，奥希替尼在 T790M 阳性患者中的疗效和安全性均相似。
