Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, South Korea.
Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
Target Oncol. 2020 Apr;15(2):185-192. doi: 10.1007/s11523-020-00706-0.
Treatment options for patients with chemotherapy-refractory solid tumors are limited.
We conducted an open-label, single-arm, single-center phase II trial to evaluate the efficacy and safety of gefitinib in patients with chemotherapy-refractory solid tumors and EGFR amplification or sensitivity to an EGFR inhibitor identified through a drug-screening platform with patient-derived tumor cells (PDCs).
EGFR amplification was detected by targeted sequencing. Sensitivity to an EGFR inhibitor was established in chemical screening using PDCs. Gefitinib (250 mg daily) was administered continuously in 28-day cycles until the occurrence of disease progression, unacceptable toxicity, or death due to any cause. The primary endpoint was the objective response rate (ORR).
In total, 15 patients were assigned to the present study. The most common tumor type was glioblastoma multiforme (n = 9, 60%), followed by gastric cancer (n = 3, 20%), anal squamous cancer, rectal cancer, and sarcoma (each n = 1, 6.7%). Among 13 evaluable patients, one patient had a partial response and five had stable disease, with an ORR of 7.7% and a disease control rate of 46.1%. The median progression-free survival was 2.1 months (95% confidence interval [CI] 0.77-3.43). The most common adverse events were diarrhea (26.7%) and skin rash (26.7%).
Gefitinib demonstrated modest anti-tumor activity and a manageable safety profile in chemotherapy-refractory solid tumors with EGFR amplification or sensitivity to an EGFR inhibitor identified through a drug-screening platform with PDCs. CLINICALTRIALS.
NCT02447419.
化疗耐药实体瘤患者的治疗选择有限。
我们进行了一项开放标签、单臂、单中心的 II 期试验，以评估吉非替尼在通过患者来源的肿瘤细胞（PDC）药物筛选平台鉴定出 EGFR 扩增或对 EGFR 抑制剂敏感的化疗耐药实体瘤患者中的疗效和安全性。
通过靶向测序检测 EGFR 扩增。使用 PDC 进行化学筛选确定对 EGFR 抑制剂的敏感性。吉非替尼（每天 250mg）在 28 天的周期中连续给药，直至疾病进展、不可接受的毒性或任何原因导致的死亡。主要终点是客观缓解率（ORR）。
共有 15 名患者被分配到本研究中。最常见的肿瘤类型是多形性胶质母细胞瘤（n=9，60%），其次是胃癌（n=3，20%）、肛门鳞状细胞癌、直肠癌和肉瘤（各 n=1，6.7%）。在 13 名可评估的患者中，1 名患者有部分缓解，5 名患者疾病稳定，ORR 为 7.7%，疾病控制率为 46.1%。中位无进展生存期为 2.1 个月（95%置信区间 [CI] 0.77-3.43）。最常见的不良事件是腹泻（26.7%）和皮疹（26.7%）。
在通过 PDC 药物筛选平台鉴定出 EGFR 扩增或对 EGFR 抑制剂敏感的化疗耐药实体瘤中，吉非替尼显示出适度的抗肿瘤活性和可管理的安全性。临床试验。
GOV 标识符：NCT02447419。
