ASCO 2012：厄洛替尼辅助治疗使EGFR突变NSCLC患者获益
2012-06-09 卢秀玲 爱唯医学网
斯坦福大学癌症研究所的Joel W. Neal博士在美国临床肿瘤学会(ASCO)年会上报告称，表皮生长因子受体(EGFR)突变型非小细胞肺癌(NSCLC)患者术后接受日常厄洛替尼辅助治疗与无病生存期持续2年以上的良好受益相关。 在这项SELECT(厄洛替尼用于EGFR突变肺
斯坦福大学癌症研究所的Joel W. Neal博士在美国临床肿瘤学会(ASCO)年会上报告称，表皮生长因子受体(EGFR)突变型非小细胞肺癌(NSCLC)患者术后接受日常厄洛替尼辅助治疗与无病生存期持续2年以上的良好受益相关。
在这项SELECT(厄洛替尼用于EGFR突变肺癌患者术后辅助治疗)研究中，研究者试图确定厄洛替尼辅助治疗能否为患者在生存率方面比常规辅助化疗(生存率通常为5%~10%)带来更大益处。EGFR突变阳性、IA~IIIA期NSCLC术后患者接受6~9个月常规辅助化疗或放化疗后，口服厄洛替尼，150 mg/d，持续 2年。对患者进行CT扫描检查随访，最初3年，1次/6个月；第4和5年，1次/年。最初入组36例患者，但因初期结果令人鼓舞，受试者最终扩至100例。
结果显示， 150 mg/d厄洛替尼维持治疗患者中位2年无病生存率达94%。目前尚未得到中位总生存率数据。仅有1例患者在接受厄洛替尼辅助治疗期间出现疾病进展，10例患者在停药6个月后出现进展，表明残余肿瘤可能对厄洛替尼再治疗敏感。对进展患者的再次活检结果显示，8例患者中有6例为同一突变，未见已知耐药机制。其中5例患者经评估可接受继续治疗，结果5例患者均对厄洛替尼再治疗敏感。然而，厄洛替尼毒性使部分患者必须降低剂量，6例患者因皮疹、腹泻和疲乏等不良事件在研究结束前终止治疗。
约翰霍普金斯大学的Michael J. Purtell博士在接受采访时评论称，在未看到长期随访结果之前，难以确信厄洛替尼辅助治疗对该类患者有益。“在不能完全肯定生存率有所改善或仅仅是无病生存率有所改善的情况下，我对酪氨酸激酶抑制剂(TKI) 2年维持治疗的毒性不敢确定。” Purtell博士未参与该项研究。
研究者总结称，截止目前的结果表明，“厄洛替尼辅助治疗至少对微转移病灶具有细胞生长抑制作用”。
题目：The SELECT study: A multicenter phase II trial of adjuvant erlotinib in resected epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC).(Abstract 7010)
作者：Joel W. Neal, Nathan A. Pennell, Ramaswamy Govindan,et al.
英文摘要
Background: Cancers with activating EGFR mutations are exquisitely sensitive to EGFR tyrosine kinase inhibitors (TKIs) and retrospective data suggests adjuvant TKIs may improve outcomes in EGFR mutants. This prospective trial investigates the safety and efficacy of adjuvant erlotinib in EGFR mutation-positive NSCLC. Methods: Patients (pts) with surgically resected stage IA-IIIA NSCLC harboring activating EGFR mutations were treated with 150 mg/day of erlotinib for 2 years (y) after completion of any standard adjuvant chemotherapy and/or radiotherapy. The trial was designed to enroll 36 patients, and powered to demonstrate a primary endpoint of 2 y disease free survival (DFS) exceeding 85%, which would suggest improvement over the historically expected 70% 2 y DFS in early stage EGFR-mutant NSCLC (J Thorac Oncol 6:569). Results: Thirty-six pts were enrolled at five sites between 1/08 and 11/09; 53% stage I; 19% stage II; 28% stage IIIA. Toxicities were typical of erlotinib; no grade 4 or 5 events or pneumonitis occurred. 8 pts (22%) required one dose reduction to 100 mg/day and 5 (14%) two reductions to 50 mg/day for grade 3 or persistent grade 2 toxicities. 11 pts discontinued before 2 full years (<1 month (mo) [4], 1-12 mo [2] and 12-23 mo [5]) for toxicities [6], patient preference [3], prostate cancer [1] and recurrence [1]. After a median follow-up of 2.5 y, the 2 y DFS from enrollment is 94% (95% CI 80%, 99%). 10 patients have recurred, 1 during erlotinib treatment and the others after stopping erlotinib (interval before recurrence 2 mo [1], 6-12 mo [4], >12 mo [4]). Genotyping on repeat biopsies from seven of the recurrent cases is underway, as is assessment of response to subsequent erlotinib therapy. Two pts have died of recurrence: one at 1.5 y who stopped erlotinib after 1 mo for toxicity, and one at 2 y who progressed while on erlotinib. Conclusions: This is the first prospective study to report the efficacy of adjuvant erlotinib in NSCLC pts with EGFR mutations. This approach is feasible and yields excellent 2y DFS compared to historical genotype-matched controls. This trial was subsequently expanded to 100 pts to permit subgroup analysis by stage.
作者：Joel W. Neal, Nathan A. Pennell, Ramaswamy Govindan,et al.
英文摘要
Background: Cancers with activating EGFR mutations are exquisitely sensitive to EGFR tyrosine kinase inhibitors (TKIs) and retrospective data suggests adjuvant TKIs may improve outcomes in EGFR mutants. This prospective trial investigates the safety and efficacy of adjuvant erlotinib in EGFR mutation-positive NSCLC. Methods: Patients (pts) with surgically resected stage IA-IIIA NSCLC harboring activating EGFR mutations were treated with 150 mg/day of erlotinib for 2 years (y) after completion of any standard adjuvant chemotherapy and/or radiotherapy. The trial was designed to enroll 36 patients, and powered to demonstrate a primary endpoint of 2 y disease free survival (DFS) exceeding 85%, which would suggest improvement over the historically expected 70% 2 y DFS in early stage EGFR-mutant NSCLC (J Thorac Oncol 6:569). Results: Thirty-six pts were enrolled at five sites between 1/08 and 11/09; 53% stage I; 19% stage II; 28% stage IIIA. Toxicities were typical of erlotinib; no grade 4 or 5 events or pneumonitis occurred. 8 pts (22%) required one dose reduction to 100 mg/day and 5 (14%) two reductions to 50 mg/day for grade 3 or persistent grade 2 toxicities. 11 pts discontinued before 2 full years (<1 month (mo) [4], 1-12 mo [2] and 12-23 mo [5]) for toxicities [6], patient preference [3], prostate cancer [1] and recurrence [1]. After a median follow-up of 2.5 y, the 2 y DFS from enrollment is 94% (95% CI 80%, 99%). 10 patients have recurred, 1 during erlotinib treatment and the others after stopping erlotinib (interval before recurrence 2 mo [1], 6-12 mo [4], >12 mo [4]). Genotyping on repeat biopsies from seven of the recurrent cases is underway, as is assessment of response to subsequent erlotinib therapy. Two pts have died of recurrence: one at 1.5 y who stopped erlotinib after 1 mo for toxicity, and one at 2 y who progressed while on erlotinib. Conclusions: This is the first prospective study to report the efficacy of adjuvant erlotinib in NSCLC pts with EGFR mutations. This approach is feasible and yields excellent 2y DFS compared to historical genotype-matched controls. This trial was subsequently expanded to 100 pts to permit subgroup analysis by stage.
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本网站所有内容来源注明为“梅斯医学”或“MedSci原创”的文字、图片和音视频资料，版权均属于梅斯医学所有。非经授权，任何媒体、网站或个人不得转载，授权转载时须注明来源为“梅斯医学”。其它来源的文章系转载文章，或“梅斯号”自媒体发布的文章，仅系出于传递更多信息之目的，本站仅负责审核内容合规，其内容不代表本站立场，本站不负责内容的准确性和版权。如果存在侵权、或不希望被转载的媒体或个人可与我们联系，我们将立即进行删除处理。
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#ASC#
72
#SCLC患者#
0
Right on-this hepeld me sort things right out.
131
#厄洛替尼#
82
#NSCLC患者#
69
#GFR#
81