厄洛替尼辅助治疗可使EGFR突变NSCLC患者受益

芝加哥(EGMN)——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”。

该研究由基因泰克公司资助，Neal博士接受了该公司提供的研究经费，Purtell博士无相关利益冲突披露。

CHICAGO (EGMN)–For patients with resected non–small cell lung cancer bearing epidermal growth factor receptor mutations, daily maintenance with erlotinib was associated with good overall disease-free survival for at least 2 years, investigators reported at the annual meeting of the American Society of Clinical Oncology.

Among 100 patients with NSCLC positive for mutations in the epidermal growth factor receptor (EGFR) who underwent surgery and routine adjuvant chemotherapy or chemoradiotherapy, maintenance with erlotinib 150 mg daily was associated with a median 2-year disease-free survival of 94%, reported Dr. Joel W. Neal of the Stanford (California) Cancer Institute.

Median overall survival has not been reached, the investigators noted in a poster session.

Only one patient had disease progression while on adjuvant erlotinib, and 10 experienced progression at least 6 months after stopping the drug, suggesting the presence of residual disease that may be sensitive to re-treatment with erlotinib, Dr. Neal said in an interview.

“We’ve encouraged repeat biopsies for patients who have progressed after treatment with adjuvant erlotinib, and of the patients who were biopsied, 6 of 8 had an identical mutation without a known mechanism of resistance,” he said.

Five of these patients were evaluable for additional therapy, and all were found to be sensitive to further treatment with erlotinib, Dr. Neal reported.

However, toxicities with erlotinib required dose reductions in some patients, and 6 patients discontinued therapy before the end of the study due to adverse events that included rash, diarrhea, and fatigue.

An oncologist who was not involved in the study commented that he would need to see longer follow-up before he could be convinced of the benefits of adjuvant erlotinib in this population.

“I’m not sure about the toxicity of 2 years of therapy with a TKI [tyrosine kinase inhibitor] in a setting where you’re not quite sure whether you’re improving survival or just disease-free survival,” said Dr. Michael J. Purtell, an assistant professor of oncology at Johns Hopkins University in Baltimore, said in an interview.

The investigators designed the study, dubbed SELECT (Surgically resected EGFR-mutant Lung cancer with adjuvant Erlotinib Cancer Treatment) to determine whether adjuvant erlotinib could provide a more robust survival benefit to patients than that afforded by conventional adjuvant chemotherapy – typically about 5-10%, they said.

Patients with EGFR mutation–positive, surgically resected stage IA-IIIA NSCLC received 6-9 months of routine adjuvant chemotherapy with or without radiation, and were then continued on oral erlotinib 150 mg daily for up to 2 years. The patients are followed with CT scans every 6 months for 3 years, then once a year for years 4 and 5.

A total of 36 patients were enrolled initially, but the study was later expanded to included 100 patients in all, after initial encouraging results.

The findings thus far suggest that “adjuvant erlotinib has, at least, a cytostatic effect on micrometastatic disease,” the investigators wrote.

The study was supported by Genentech. Dr. Neal has received research funding from the company. Dr. Purtell had no relevant disclosures.