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一线使用不可逆的酪氨酸激酶抑制剂与 EGFR 突变阳性非小细胞肺癌的 OS 延长相关。

First-line treatment with irreversible tyrosine kinase inhibitors associated with longer OS in EGFR mutation-positive non-small cell lung cancer.

机构信息

Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.

Department of Nursing, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.

出版信息

Thorac Cancer. 2021 Feb;12(3):287-296. doi: 10.1111/1759-7714.13462. Epub 2020 Dec 18.

Abstract

BACKGROUND

Few studies have compared the efficacy of the irreversible epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), afatinib, with that of reversible EGFR-TKIs. Therefore, this study assessed the effectiveness of afatinib, erlotinib, and gefitinib in terms of OS (overall survival) and progression-free survival (PFS) in EGFR mutation-positive advanced non-small cell lung cancer (NSCLC) patients.

METHODS

Patients with EGFR mutation-positive advanced NSCLC who sought treatment from December 2013 to June 2018, at a tertiary referral center were retrospectively analyzed. These patients were treated with afatinib or a reversible EGFR-TKI (erlotinib or gefitinib) until disease progression, intolerable adverse events, or death. The Kaplan-Meier and log-rank tests were then used to compare the OS and PFS of the patients. We further analyzed the survival differences among the subgroup of patients without brain metastases.

RESULTS

Of the 363 patients enrolled, 134 and 229 received first-line afatinib and first-line reversible EGFR-TKI, respectively. Those given afatinib had better OS (39.3 vs. 26.0 months; HR 0.65, P = 0.033) and PFS (14.1 vs.11.2 months; HR 0.58, P < 0.001). Of the 246 patients without brain metastases, 93 and 153 received first-line afatinib and a first-line reversible EGFR-TKI, respectively. Those given afatinib had a better OS (52.6 vs. 24.9 months; HR 0.62, P = 0.0030) and PFS (17.7 vs. 11.1 months; HR 0.51, P < 0.001). The survival benefit was more significant in the subgroup of patients with L858R substitutions.

CONCLUSIONS

The results indicated that afatnib resulted in significantly better OS and PFS than gefitnib and erlotinib for EGFR mutation-positive advanced NSCLC patients without brain metastases.

KEY POINTS

Significant findings of the study Afatnib resulted in significantly better overall survival and progression-free survival than gefitnib and erlotinib for EGFR mutation-positive advanced non-small cell lung cancer patients without brain metastases. What this study adds This study helps fill the gap in our limited understanding of the differences in the efficacy of the irreversible epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), afatinib, with that of reversible EGFR-TKIs.

摘要

背景

鲜有研究比较不可逆表皮生长因子受体酪氨酸激酶抑制剂(EGFR-TKI)阿法替尼与可逆 EGFR-TKI 的疗效。因此,本研究旨在评估阿法替尼、厄洛替尼和吉非替尼在 EGFR 突变阳性晚期非小细胞肺癌(NSCLC)患者中的总生存期(OS)和无进展生存期(PFS)方面的疗效。

方法

回顾性分析 2013 年 12 月至 2018 年 6 月在一家三级转诊中心接受治疗的 EGFR 突变阳性晚期 NSCLC 患者。这些患者接受阿法替尼或可逆 EGFR-TKI(厄洛替尼或吉非替尼)治疗,直至疾病进展、无法耐受的不良事件或死亡。然后,采用 Kaplan-Meier 法和对数秩检验比较患者的 OS 和 PFS。我们进一步分析了无脑转移亚组患者的生存差异。

结果

共纳入 363 例患者,其中 134 例患者接受一线阿法替尼治疗,229 例患者接受一线可逆 EGFR-TKI 治疗。接受阿法替尼治疗的患者 OS(39.3 个月 vs. 26.0 个月;HR 0.65,P = 0.033)和 PFS(14.1 个月 vs. 11.2 个月;HR 0.58,P < 0.001)均更佳。在 246 例无脑转移患者中,93 例患者接受一线阿法替尼治疗,153 例患者接受一线可逆 EGFR-TKI 治疗。接受阿法替尼治疗的患者 OS(52.6 个月 vs. 24.9 个月;HR 0.62,P = 0.0030)和 PFS(17.7 个月 vs. 11.1 个月;HR 0.51,P < 0.001)均更佳。在 L858R 取代亚组患者中,生存获益更为显著。

结论

研究结果表明,对于无脑转移的 EGFR 突变阳性晚期 NSCLC 患者,阿法替尼的 OS 和 PFS 显著优于吉非替尼和厄洛替尼。

关键要点

研究的重要发现:对于无脑转移的 EGFR 突变阳性晚期非小细胞肺癌患者,阿法替尼的总生存期和无进展生存期显著优于吉非替尼和厄洛替尼。本研究的意义:本研究有助于填补我们对不可逆表皮生长因子受体酪氨酸激酶抑制剂(EGFR-TKI)阿法替尼与可逆 EGFR-TKI 疗效差异的认识空白。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a045/7862787/a94c7abf3668/TCA-12-287-g001.jpg

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