Department of Thoracic Medical Oncology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-8-31, Ariake, Koto-ku, Tokyo, 135-8550, Japan.
Department of Thoracic Medical Oncology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-8-31, Ariake, Koto-ku, Tokyo, 135-8550, Japan; Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, 3-8-31, Ariake, Koto-ku, Tokyo, 135-8550, Japan; Department of Respiratory Medicine, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.
Lung Cancer. 2018 Mar;117:1-6. doi: 10.1016/j.lungcan.2017.12.018. Epub 2018 Jan 4.
Osimertinib is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor that can overcome resistance due to the Thr790Met (T790M) mutation. However, osimertinib occasionally shows limited efficacy in a small population of patients. We investigated the correlation between the ratio of T790M to EGFR activating mutation and the response to osimertinib.
Between April 2016 and April 2017, 44 patients started osimertinib therapy at the Cancer Institute Hospital of the Japanese Foundation for Cancer Research. We performed EGFR mutation analysis of cytological samples from 33 patients using droplet digital PCR. We calculated the ratio of T790M to EGFR activating mutations and correlated it with the systemic response to osimertinib.
In tumors from the 33 patients, the average ratio of T790M to EGFR activating mutations was 0.420. Twenty-one of the 33 patients had tumors with a T790M ratio of ≥0.4. The osimertinib response rate was significantly higher (92.3%) in patients with a T790M ratio of ≥0.4 than in those with a T790M ratio of <0.4 (52.6%; p = 0.0237). We examined the correlation between the T790M ratio and the tumor reduction rate and obtained a coefficient of r = 0.417 (p = 0.0175). In patients with a T790M ratio of ≥0.4, the median progression-free survival was 355 days, which was longer, but not significant, than that in patients with a T790M ratio of <0.4 (median: 264 days). In patients with a T790M ratio of ≥0.4, the median treatment duration from first-line therapy onward was 931 days, which was significantly longer than that in patients with a T790M ratio of <0.4 (median, 567.5 days) (p = 0.044).
The T790M ratio to EGFR activating mutation in tumor may correlate with the response to osimertinib, and patients with a higher T790M ratio have a longer treatment history.
奥希替尼是一种第三代表皮生长因子受体（EGFR）酪氨酸激酶抑制剂，可克服因 Thr790Met（T790M）突变而产生的耐药性。然而，奥希替尼在一小部分患者中的疗效有限。我们研究了 T790M 与 EGFR 激活突变的比值与奥希替尼反应之间的相关性。
2016 年 4 月至 2017 年 4 月，日本癌症基金会癌症研究所的 44 名患者开始接受奥希替尼治疗。我们使用液滴数字 PCR 对 33 名患者的细胞学样本进行了 EGFR 突变分析。我们计算了 T790M 与 EGFR 激活突变的比值，并将其与奥希替尼的全身反应相关联。
在 33 名患者的肿瘤中，T790M 与 EGFR 激活突变的平均比值为 0.420。33 名患者中有 21 名患者的肿瘤 T790M 比值≥0.4。T790M 比值≥0.4 的患者奥希替尼的应答率明显高于 T790M 比值<0.4 的患者（92.3% vs. 52.6%；p=0.0237）。我们检验了 T790M 比值与肿瘤缩小率之间的相关性，得到 r 值为 0.417（p=0.0175）。在 T790M 比值≥0.4 的患者中，无进展生存期的中位数为 355 天，虽然更长，但无显著差异，而 T790M 比值<0.4 的患者为 264 天（中位数）（p=0.0175）。在 T790M 比值≥0.4 的患者中，自一线治疗开始的中位治疗持续时间为 931 天，明显长于 T790M 比值<0.4 的患者（中位数为 567.5 天）（p=0.044）。
肿瘤中 T790M 与 EGFR 激活突变的比值可能与奥希替尼的反应相关，而 T790M 比值较高的患者具有更长的治疗史。
