Department of Thoracic Medical Oncology, the Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.
Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University, Saga, Japan.
Invest New Drugs. 2022 Dec;40(6):1342-1349. doi: 10.1007/s10637-022-01301-y. Epub 2022 Sep 24.
Data on the re-administration of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) after osimertinib failure in patients with T790M-positive non-small cell lung cancer (NSCLC) is limited. EGFR-TKI re-administration efficacy may vary between patients with T790M loss and those with T790M persistent with re-biopsy after osimertinib treatment. Patients who received EGFR-TKI re-administration (gefitinib, erlotinib, afatinib, dacomitinib, and osimertinib) after osimertinib failure were identified from our database. T790M mutation status before EGFR-TKI re-administration was analyzed via repeat biopsy. We retrospectively evaluated the efficacy of EGFR-TKI re-administration, especially differences according to the T790M mutation status, via repeat biopsy. Until June 2020, 28 patients received EGFR-TKI re-administration and 17 underwent repeat biopsy after osimertinib failure. Patients were divided into three groups, including the T790M loss group, where active mutation persisted and T790M was lost (13/17); T790M remaining group, where both the active mutation and T790M persisted (3/17); and active mutation loss group where both the active mutation and T790M were lost (1/17). The overall response rate (ORR) of EGFR-TKI re-administration in the T790M loss group was 31% and the disease control rate (DCR) was 54%, which were higher than the ORR of 21% and DCR of 43% in the entire patient population. ORR and DCR of the not re-biopsy group were low (9% and 27%, respectively). The therapeutic effect of EGFR-TKI re-administration in patients with T790M-positive NSCLC after osimertinib failure is limited. EGFR-TKI re-administration may be considered in cases of T790M loss after repeat biopsy.
奥希替尼治疗后 T790M 阳性非小细胞肺癌（NSCLC）患者再次使用表皮生长因子受体（EGFR）-酪氨酸激酶抑制剂（TKI）的数据有限。奥希替尼治疗后再次活检时 T790M 丢失与 T790M 持续存在的患者之间，EGFR-TKI 再治疗的疗效可能不同。我们从数据库中确定了奥希替尼治疗失败后接受 EGFR-TKI 再治疗（吉非替尼、厄洛替尼、阿法替尼、达可替尼和奥希替尼）的患者。通过重复活检分析 EGFR-TKI 再治疗前的 T790M 突变状态。我们回顾性评估了 EGFR-TKI 再治疗的疗效，特别是根据重复活检的 T790M 突变状态的差异。截至 2020 年 6 月，28 例患者接受了 EGFR-TKI 再治疗，17 例患者在奥希替尼治疗失败后进行了重复活检。患者分为三组，包括 T790M 丢失组，其中活性突变持续存在且 T790M 丢失（13/17）；T790M 持续存在组，其中活性突变和 T790M 均持续存在（3/17）；以及活性突变丢失组，其中活性突变和 T790M 均丢失（1/17）。T790M 丢失组的 EGFR-TKI 再治疗总缓解率（ORR）为 31%，疾病控制率（DCR）为 54%，高于整个患者人群的 ORR（21%）和 DCR（43%）。未行重复活检组的 ORR 和 DCR 较低（分别为 9%和 27%）。奥希替尼治疗后 T790M 阳性 NSCLC 患者再次使用 EGFR-TKI 的疗效有限。在重复活检后 T790M 丢失的情况下，可考虑再次使用 EGFR-TKI 治疗。
