厄洛替尼对比观察用于一线含铂化疗后无疾病进展证据的卵巢癌患者的随机 III 期研究：欧洲癌症研究与治疗组织妇科肿瘤组和妇科肿瘤协作组研究。

Randomized phase III study of erlotinib versus observation in patients with no evidence of disease progression after first-line platin-based chemotherapy for ovarian carcinoma: a European Organisation for Research and Treatment of Cancer-Gynaecological Cancer Group, and Gynecologic Cancer Intergroup study.

机构信息

Ignace B. Vergote and Evelyn Despierre, University Hospitals Leuven and Katholieke Universiteit Leuven, Leuven; Corneel Coens, European Organisation for Research and Treatment of Cancer Headquarters, Brussels, Belgium; Antonio Jimeno, University of Colorado School of Medicine, Aurora, CO; Florence Joly, Centre François Baclesse Caen, Caen; Anne Lesoin, Centre Oscar Lambret, Lille; Isabelle Ray-Coquard, Centre Léon Bérard, Lyon; Laure Favier, Centre Georges François Leclerc, Dijon; Hervé Curé, Unicancer Institut Jean Godinot, Reims; Eric Pujade-Lauraine, Hôpital Hôtel-Dieu, Paris, France; Dionyssios Katsaros, University of Turin; Annamaria Ferrero, Ospedale Mauriziano Umberto I, Turin; Nicoletta Colombo, University of Milan-Bicocca and Istituto Europeo di Oncologia, Milan, Italy; Christian Marth, Medical University of Innsbruck, Innsbruck; Alexander Reinthaller, Medical University of Vienna, Vienna, Austria; Marcia Hall, Mount Vernon Cancer Centre, Middlesex; John Green, University of Liverpool, Liverpool; Nick Simon Reed, Gartnavel General Hospitals, Glasgow, United Kingdom; Christopher B. Steer, Border Medical Oncology, Wodonga; Martin Buck, Government of Western Australia, Department of Health, Perth, Australia; and Antonio Casado, Universitario San Carlos, Madrid, Spain.

出版信息

J Clin Oncol. 2014 Feb 1;32(4):320-6. doi: 10.1200/JCO.2013.50.5669. Epub 2013 Dec 23.

DOI:10.1200/JCO.2013.50.5669

PMID:24366937

Abstract

PURPOSE

This trial evaluated the efficacy of maintenance erlotinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, after first-line chemotherapy.

PATIENTS AND METHODS

Eligible patients had high-risk International Federation of Gynecology and Obstetrics stage I or stage II to IV epithelial ovarian, primary peritoneal, or fallopian tube cancer and were not selected for EGFR expression. All patients underwent first-line platinum-based chemotherapy (CT) and showed no signs of progression at the end of CT. Patients were randomly assigned to maintenance erlotinib 150 mg orally daily for 2 years or to observation. EGFR immunohistochemistry (IHC), fluorescent in situ hybridization (FISH), and mutation analyses were performed in 318 patients.

RESULTS

Between October 2005 and February 2008, 835 patients were randomly assigned (median follow-up, 51 months). Twenty-six percent of the patients stopped erlotinib as a result of adverse effects (of these, 67% were due to rash). For erlotinib and observation, respectively, the median progression-free survival was 12.7 and 12.4 months (hazard ratio [HR], 1.05; 95% CI, 0.90 to 1.23), and the median overall survival was 50.8 and 59.1 months (HR, 0.99; 95% CI, 0.81 to 1.20 months), respectively. No subgroup could be identified with improved effect of erlotinib, based on IHC or FISH for EGFR, or mutations in genes related to the EGFR pathway, or on rash during erlotinib therapy. However, patients with a positive FISH EGFR score had a worse overall survival (46.1 months) than those with a negative score (67.0 months; HR, 1.56; 95% CI, 1.01 to 2.40; P = .044). Global health/quality-of-life scores showed a significant difference during the first year (P = .0102) in favor of the observation arm.

CONCLUSION

Maintenance erlotinib after first-line treatment in ovarian cancer did not improve progression-free or overall survival.

摘要

目的

本试验评估了表皮生长因子受体（EGFR）酪氨酸激酶抑制剂厄洛替尼维持治疗在一线化疗后的疗效。

患者和方法

符合条件的患者为国际妇产科联合会（FIGO）高危Ⅰ期或Ⅱ-Ⅳ期上皮性卵巢癌、原发性腹膜癌或输卵管癌，且未选择 EGFR 表达。所有患者均接受一线含铂化疗（CT），且 CT 结束时无进展迹象。患者被随机分配至厄洛替尼 150 mg 每日口服维持治疗 2 年或观察。对 318 例患者进行 EGFR 免疫组化（IHC）、荧光原位杂交（FISH）和突变分析。

结果

2005 年 10 月至 2008 年 2 月，835 例患者被随机分配（中位随访 51 个月）。26%的患者因不良反应（其中 67%为皮疹）停止厄洛替尼治疗。厄洛替尼组和观察组的中位无进展生存期分别为 12.7 个月和 12.4 个月（风险比 [HR]，1.05；95%CI，0.90 至 1.23），中位总生存期分别为 50.8 个月和 59.1 个月（HR，0.99；95%CI，0.81 至 1.20 个月）。根据 EGFR 的 IHC 或 FISH 以及与 EGFR 通路相关基因的突变，或厄洛替尼治疗期间的皮疹，均未确定厄洛替尼疗效改善的亚组。然而，FISH EGFR 阳性评分的患者总生存期较差（46.1 个月），阴性评分的患者总生存期较好（67.0 个月；HR，1.56；95%CI，1.01 至 2.40；P =.044）。整体健康/生活质量评分在第一年（P =.0102）有显著差异，观察组更有利。