Efficacy of gefitinib in patients with advanced non-small cell carcinoma of the lung harboring common, uncommon and complex EGFR mutations

W. Kwok, K. Chiang, J. Ho, T. Tam, M. Ip, D. Lam
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Abstract

As the commonest EGFR-TKI being used in Hong Kong, gefitinib has shown to be efficacious and safe as first line treatment for L858R mutation and exon 19 deletion with less gastrointestinal and cutaneous adverse events than erlotinib and afatinib. However, the evidence for therapeutic efficacy for uncommon and complex EGFR mutations is lacking. Whether gefitinib is efficacious for uncommon and complex EGFR mutations worth studying. To assess the therapeutic efficacy of gefitinib, as measured by progression-free survival and overall survival, among advanced stage lung cancer patients with common, uncommon and complex EGFR mutations. This is a retrospective cohort study that included 241 Chinese patients with advanced non-small cell carcinoma of lung harboring EGFR mutations and received gefitinib 250 mg daily as first-line treatment. The progression-free survival [PFS] and overall survival [OS] for patients with different EGFR mutations, namely exon 19 deletion, L858R mutation in exon 21, uncommon EGFR mutations and complex EGFR mutations were analyzed. Among the 241 patients, 118 [49%] had exon 19 deletion, 104 [43%] had L858R mutation in exon 21, 6 [2.5%] had uncommon EGFR mutations, 13 [5.4%] had complex EGFR mutations. The mean age was 69. 72% of the patients were female and with 81% being non-smoker. For patients with complex EGFR mutations, regardless of the presence of exon 19 deletion and L858R mutation as the component, have better PFS and OS than patients with single common EGFR mutations [Exon 19 deletion or L858R mutation]. Patients with uncommon EGFR mutations have inferior PFS and OS than those with common EGFR mutations. Gefitinib is a possible option for patients with complex EGFR mutations while it may not be the preferred treatment option in patients with single uncommon EGFR mutations.
吉非替尼对携带常见、罕见和复杂EGFR突变的晚期非小细胞肺癌患者的疗效
作为香港最常见的EGFR-TKI,吉非替尼作为L858R突变和外显子19缺失的一线治疗已被证明是有效和安全的,与埃洛替尼和阿法替尼相比,胃肠道和皮肤不良事件更少。然而,缺乏对罕见和复杂的EGFR突变具有疗效的证据。吉非替尼是否对罕见和复杂的EGFR突变有效值得研究。评估吉非替尼在具有常见、罕见和复杂EGFR突变的晚期癌症患者中的治疗效果,以无进展生存率和总生存率衡量。这是一项回顾性队列研究,纳入241名携带EGFR突变的晚期非小细胞肺癌中国患者,并接受吉非替尼250 mg每日一线治疗。分析了具有不同EGFR突变(即外显子19缺失、外显子21中的L858R突变、罕见EGFR突变和复杂EGFR突变)的患者的无进展生存期[PFS]和总生存期[OS]。在241名患者中,118名[49%]患者的外显子19缺失,104名[43%]患者外显子21中有L858R突变,6名[2.5%]患者的EGFR突变不常见,13名[5.4%]患者有复杂的EGFR变异。平均年龄69岁。72%的患者为女性,81%的患者为非吸烟者。对于具有复杂EGFR突变的患者,无论是否存在外显子19缺失和L858R突变作为成分,其PFS和OS都比具有单一常见EGFR突变[外显子十九缺失或L858R]的患者更好。与具有常见EGFR突变的患者相比,具有罕见EGFR突变患者的PFS和OS较差。吉非替尼是复杂EGFR突变患者的一种可能选择,而对于单一不常见EGFR突变的患者,它可能不是首选治疗方案。
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