Increased epidermal growth factor receptor gene copy number detected by fluorescence in situ hybridization associates with increased sensitivity to gefitinib in patients with bronchioloalveolar carcinoma subtypes: A Southwest Oncology Group Study
Increased epidermal growth factor receptor gene copy number detected by fluorescence in situ hybridization associates with increased sensitivity to gefitinib in patients with bronchioloalveolar carcinoma subtypes: A Southwest Oncology Group Study
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DOI：
10.1200/jco.2005.01.2823
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发表时间：
2005-10-01
影响因子：
45.3
通讯作者：
Gandara, DR
中科院分区：
文献类型：
--
作者：
Hirsch, FR;Varella-Garcia, M;Gandara, DR
目的细支气管肺泡癌（BAC）和具有BAC特征的腺癌的发病率似乎正在增加，特别是在年轻、从不吸烟的女性中。表皮生长因子受体（EGFR）抑制剂在晚期BAC亚型患者中显示出20%至30%的缓解率，但患者治疗的选择方法尚未建立。采用荧光原位杂交（FISH）技术对81例接受吉非替尼500 mg/d（西南肿瘤组方案S0126）治疗的患者的EGFR和HER2基因拷贝数进行评估，并与治疗结果进行相关性分析。肿瘤分为两大类：fish阳性（高多体/基因扩增）和fish阴性（二体/低多体）。结果81例患者中，EGFR/ fish阴性患者的中位生存时间为8个月，而fish阳性患者的中位生存时间尚未达到（但接近18个月；风险比[HR] = 2.02; P = 0.042）。EGFR/ fish阳性患者的中位无进展生存期为9个月，而fish阴性患者的中位无进展生存期为4个月（HR = 1.67; P = 0.072）。在多变量分析中，在考虑吸烟状况、性别、组织学和表现状况后，FISH的EGFR拷贝数仍然是生存率的重要预测因素。使用实体瘤组应答评价标准对55例患者进行应答评价，19例EGFR/ fish阳性患者中有12例（63%）表现出疾病控制，而fish阴性组中36例患者中有14例（39%）表现出疾病控制（P = 0.087）。HER2基因拷贝数与应答（n = 39例）或生存（n = 56例，P < 0.05）无相关性。10)。结论FISH检测到EGFR基因拷贝数增加与吉非替尼治疗后晚期BAC患者生存率提高相关，提示FISH方法可用于评估EGFR酪氨酸激酶抑制剂治疗患者的生存潜力。荧光原位杂交检测表皮生长因子受体基因拷贝数增加与细支气管肺泡癌亚型患者对吉非替尼敏感性增加相关：西南肿瘤组研究
Purpose Bronchioloalveolar carcinoma (BAC) and adenocarcinomas with BAC features seem to be increasing in incidence, particularly in younger, never-smoking women. Epidermal growth factor receptor (EGFR) inhibitors demonstrated response rates of 20% to 30% in patients with advanced BAC subtypes, but selection methods for patient therapy are not established.Patients and Methods EGFR and HER2 gene copy numbers were assessed by fluorescence in situ hybridization (FISH) in 81 patients treated with gefitinib 500 mg/d (Southwest Oncology Group protocol S0126) and were correlated to treatment outcome. Tumors were classified into two main strata: FISH-positive (high polysomy/gene amplification) and FISH-negative (disomy/low polysomy).Results In 81 patients, the median survival time for EGFR/FISH-negative patients was 8 months and not yet reached for FISH-positive patients (but approaching 18 months; hazard ratio [HR] = 2.02; P =.042). Median progression-free survival time for EGFR/FISH-positive patients was 9 months versus 4 months for the FISH-negative patients (HR = 1.67; P =.072). In multivariate analysis, EGFR copy number by FISH remained a significant predictive factor for survival after accounting for smoking status, sex, histology, and performance status. Fifty-five patients were evaluated for response using Response Evaluation Criteria in Solid Tumors Group, and 12 of 19 EGFR/FISH-positive patients (63%) demonstrated disease control versus 14 (39%) of 36 patients in the FISH-negative group (P =.087). No association was found between HER2 gene copy number and response (n = 39 patients) or survival (n = 56 patients, P >. 10).Conclusion Increased EGFR gene copy number detected by FISH is associated with improved survival after gefitinib therapy in patients with advanced BAC, suggesting FISH methodology can be used to assess survival potential in patients treated with EGFR tyrosine kinase inhibitors.Increased Epidermal Growth Factor Receptor Gene Copy Number Detected by Fluorescence In Situ Hybridization Associates With Increased Sensitivity to Gefitinib in Patients With Bronchioloalveolar Carcinoma Subtypes: A Southwest Oncology Group Study.