Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA.
Division of General Internal Medicine and Health Services Research, Department of Medicine Statistics Core, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA.
Clin Lung Cancer. 2018 Jan;19(1):e19-e28. doi: 10.1016/j.cllc.2017.06.004. Epub 2017 Jun 20.
The secondary T790M mutation accounts for more than 50% of acquired tyrosine kinase inhibitor (TKI) resistance in patients with EGFR-mutated non-small-cell lung cancer (NSCLC). Recent reports suggest this resistance mutation may be more common among patients with longer progression-free survival (PFS) on first-line TKI therapy, but much is still unknown.
Our group collected medical records from patients who underwent a biopsy for T790M mutation testing while screening for clinical trials involving the drug rociletinib (CO-1686), a T790M mutation-specific TKI. Medical records were retrospectively analyzed for demographic data, PFS, and best response to previous therapies.
Our patient cohort included 69 T790M patients and 28 T790M patients. Patients who later developed a T790M mutation had a longer PFS on first-line TKI therapy (12.0 vs. 9.0 months, P = .021), but overall response rate (ORR) was the same (75.0% vs. 81.0%, P = .76). There was no difference in PFS on TKI rechallenge (4.0 vs. 3.0 months, P = .94), although there was a trend toward higher ORR in T790M patients (22.2% vs. 0%, P = .12). T790M patients had a longer PFS on initial chemotherapy treatment (5.0 vs. 4.0 months, P = .025) and a trend toward higher ORR (40.0% vs. 21.4%, P = .31).
Our study confirms that tumors expressing T790M have a more indolent progression of disease compared with their T790M counterparts when treated with both first-line TKI and cytotoxic chemotherapy.
继发性 T790M 突变占 EGFR 突变型非小细胞肺癌（NSCLC）患者获得性酪氨酸激酶抑制剂（TKI）耐药的 50%以上。最近的报告表明，这种耐药突变在一线 TKI 治疗中无进展生存期（PFS）较长的患者中更为常见，但仍有许多未知之处。
我们的团队从接受 T790M 突变检测的患者的病历中收集了数据，这些患者在筛选涉及药物 Rociletinib（CO-1686）的临床试验时进行了检测，Rociletinib 是一种针对 T790M 突变的 TKI。对病历进行回顾性分析，以获取人口统计学数据、PFS 和之前治疗的最佳反应。
我们的患者队列包括 69 名 T790M 患者和 28 名 T790M 患者。随后发生 T790M 突变的患者在一线 TKI 治疗中的 PFS 更长（12.0 与 9.0 个月，P =.021），但总缓解率（ORR）相同（75.0%与 81.0%，P =.76）。在 TKI 再挑战时，PFS 没有差异（4.0 与 3.0 个月，P =.94），尽管 T790M 患者的 ORR 有升高趋势（22.2%与 0%，P =.12）。T790M 患者在初始化疗治疗中的 PFS 更长（5.0 与 4.0 个月，P =.025），ORR 有升高趋势（40.0%与 21.4%，P =.31）。
我们的研究证实，与 T790M 表达的肿瘤相比，T790M 表达的肿瘤在接受一线 TKI 和细胞毒化疗治疗时，疾病进展更为缓慢。
