A phase II trial of induction of erlotinib followed by cytotoxic chemotherapy for EGFR mutation-positive non-squamous non-small cell lung cancer patients.
A phase II trial of induction of erlotinib followed by cytotoxic chemotherapy for EGFR mutation-positive non-squamous non-small cell lung cancer patients.
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对 EGFR 突变阳性非鳞状非小细胞肺癌患者进行厄洛替尼诱导后进行细胞毒性化疗的 II 期试验。
DOI：
10.1007/s00280-019-03934-y
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发表时间：
2019
期刊：
影响因子：
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通讯作者：
Soejima K.
中科院分区：
文献类型：
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作者：
Tani T;Naoki K;Yasuda H;Arai D;Ishioka K;Ohgino K;Yoda S;Nakayama S;Satomi R;Terai H;Ikemura S;Sato T;Soejima K.
对于表皮生长因子受体酪氨酸激酶抑制剂(EGFR-TKI)和细胞毒性化疗治疗EGFR突变阳性的非小细胞肺癌(NSCLC)患者的治疗顺序和时机尚未达成共识。方法在这项II期试验中，纳入了未接受化疗且EGFR基因突变激活的IIIB/IV期或手术后复发的非小细胞肺癌患者。患者接受厄洛替尼诱导，150 mg/d，连续3个月。之后，当诱导的厄洛替尼达到CR或PR时，再用铂加培美曲塞进行细胞毒化疗，无论有没有贝伐单抗。主要终点是1年无进展生存率(PFS)，次要终点是有效率(RR)、无进展生存率(PFS)、安全性和总生存率(OS)。年龄中位数为63岁。其中IV期18例，复发2例。11名患者在厄洛替尼诱导后获得PR，其中9名患者转为化疗。意向治疗(ITT)人群1年PFS率为45.0%(90%可信区间为26.8-63.2)，总RR为55.0%，中位PFS为10.7个月。40%的患者报告了3-4级不良事件，包括白细胞减少(10%)、中性粒细胞减少(20%)、间质性肺炎、细菌性肺炎、皮疹和恶心(均为5%)。然而，该疗法耐受性良好，可能成为未来对短期厄洛替尼治疗有效的患者进行研究的一种治疗选择。临床试验注册编号UMIN ID：000013125。
BackgroundNo consensus has been reached regarding the treatment order and timing of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) and cytotoxic chemotherapy administration for EGFR mutation-positive non-small cell lung cancer (NSCLC) patients.MethodsIn this phase II trial, chemotherapy-naïve patients harboring activating EGFR mutations with stage IIIB/IV or post-surgical recurrent non-squamous NSCLC were enrolled. Patients were treated with erlotinib induction at 150 mg/day for 3 months. This was followed by cytotoxic chemotherapy with platinum plus pemetrexed, with or without bevacizumab, when the induction erlotinib achieved a CR or PR. The primary end point was the 1-year progression-free survival (PFS) rate, while the secondary end points were the response rate (RR), PFS, safety, and overall survival (OS).ResultsTwenty patients were enrolled in this study. The median age was 63 years. Eighteen patients had stage IV disease, and 2 patients had recurrent disease. Eleven patients achieved a PR after induction of erlotinib and 9 out of 11 patients were switched to chemotherapy. The 1-year PFS rate was 45.0% (90% CI 26.8–63.2), the overall RR was 55.0%, and the median PFS was 10.7 months in the intention-to-treat (ITT) population. Grade 3–4 adverse events were reported for 40% of the patients, including patients with leukopenia (10%), neutropenia (20%), and interstitial pneumonitis, bacterial pneumonia, rash, and nausea (all 5%).ConclusionsThe primary end point of this study was not achieved. However, the therapy was well tolerated and may be a treatment option for a future study with patients responsive to short-term erlotinib treatment.Clinical trials registration numberUMIN ID: 000013125.