Division of Hematology/Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
Lowe Center for Thoracic Oncology, The Belfer Institute for Applied Cancer Science, Dana-Farber Cancer Institute, Boston, Massachusetts.
Cancer. 2021 May 1;127(9):1407-1416. doi: 10.1002/cncr.33385. Epub 2021 Jan 12.
In this open-label, international phase 2 study, the authors assessed the efficacy and safety of olmutinib in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) who had a confirmed T790M mutation and disease progression on previous epidermal growth factor receptor-tyrosine kinase inhibitor therapy.
Patients aged ≥20 years received once-daily oral olmutinib 800 mg continuously in 21-day cycles. The primary endpoint was the objective response rate (patients who had a confirmed best overall response of a complete or partial response), assessed by central review. Secondary endpoints included the disease control rate, the duration of objective response, progression-free survival, and overall survival. Adverse events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.03).
Overall, 162 patients (median age, 63 years; women, >60%) were enrolled from 68 sites in 9 countries. At the time of database cutoff, 23.5% of enrolled patients remained on treatment. The median treatment duration was 6.5 months (range, 0.03-21.68 months). Overall, 46.3% of patients (95% CI, 38.4%-54.3%) had a confirmed objective response (all partial responses). The best overall response (the objective response rate regardless of confirmation) was 51.9% (84 patients; 95% CI, 43.9%-59.8%). The confirmed disease control rate for all patients was 86.4% (95% CI, 80.2%-91.3%). The median duration of objective response was 12.7 months (95% CI, 8.3-15.4 months). Estimated median progression-free survival was 9.4 months (95% CI, 6.9-12.3 months), and estimated median overall survival was 19.7 months (95% CI, 15.1 months to not reached). All patients experienced treatment-emergent adverse events, and 71.6% of patients had grade ≥3 treatment-emergent adverse events.
Olmutinib has meaningful clinical activity and a manageable safety profile in patients with T790M-positive non-small cell lung cancer who received previous epidermal growth factor receptor-tyrosine kinase inhibitor therapy.
在这项开放标签、国际 2 期研究中，作者评估了 olmutinib 在先前表皮生长因子受体酪氨酸激酶抑制剂治疗后疾病进展且有确认的 T790M 突变的局部晚期或转移性非小细胞肺癌（NSCLC）患者中的疗效和安全性。
年龄≥20 岁的患者接受每日一次口服 olmutinib 800mg，连续 21 天为一个周期。主要终点是由中心审查确认的客观缓解率（患者的最佳总缓解为完全或部分缓解）。次要终点包括疾病控制率、客观缓解持续时间、无进展生存期和总生存期。根据国家癌症研究所不良事件通用术语标准（4.03 版）对不良事件进行分级。
总体而言，来自 9 个国家 68 个地点的 162 名患者（中位年龄 63 岁；女性＞60%）入组。在数据截止时，23.5%的入组患者仍在接受治疗。中位治疗持续时间为 6.5 个月（范围：0.03-21.68 个月）。总体而言，46.3%的患者（95%CI：38.4%-54.3%）有确认的客观缓解（均为部分缓解）。最佳总缓解率（无论确认与否的客观缓解率）为 51.9%（84 例；95%CI：43.9%-59.8%）。所有患者的确认疾病控制率为 86.4%（95%CI：80.2%-91.3%）。客观缓解持续时间的中位值为 12.7 个月（95%CI：8.3-15.4 个月）。估计中位无进展生存期为 9.4 个月（95%CI：6.9-12.3 个月），估计中位总生存期为 19.7 个月（95%CI：15.1 个月至未达到）。所有患者均发生治疗相关不良事件，71.6%的患者有≥3 级治疗相关不良事件。
在先前接受表皮生长因子受体酪氨酸激酶抑制剂治疗后有 T790M 阳性非小细胞肺癌的患者中，olmutinib 具有显著的临床活性和可控的安全性。
