贝伐单抗、培美曲塞和顺铂，或贝伐单抗与厄洛替尼用于经表皮生长因子受体突变分层的晚期非小细胞肺癌患者：II期试验SAKK19/09
Bevacizumab, Pemetrexed, and Cisplatin, or Bevacizumab and Erlotinib for Patients With Advanced Non-Small-Cell Lung Cancer Stratified by Epidermal Growth Factor Receptor Mutation: Phase II Trial SAKK19/09.
作者信息
Gautschi Oliver, Mach Nicholas, Rothschild Sacha I, Li Qiyu, Stahel Rolf A, Zippelius Alfred, Cathomas Richard, Früh Martin, Betticher Daniel C, Peters Solange, Rauch Daniel, Feilchenfeldt Jonas, Bubendorf Lukas, Savic Spasenija, Jaggi Rolf, Leibundgut Elisabeth Oppliger, Largiadèr Carlo, Brutsche Martin, Pilop Christiane, Stalder Lukas, Pless Miklos, Ochsenbein Adrian F
机构信息
Medical Oncology, Cantonal Hospital Luzern, Luzern, Switzerland.
Clinical Research Unit of the Dr. Dubois-Ferrière Dinu Lipatti Foundation, Oncology Center, Geneva University Hospital, Geneva, Switzerland.
出版信息
Clin Lung Cancer. 2015 Sep;16(5):358-65. doi: 10.1016/j.cllc.2015.02.007. Epub 2015 Mar 5.
OBJECTIVE
The goal was to demonstrate that tailored therapy, according to tumor histology and epidermal growth factor receptor (EGFR) mutation status, and the introduction of novel drug combinations in the treatment of advanced non-small-cell lung cancer are promising for further investigation.
METHODS
We conducted a multicenter phase II trial with mandatory EGFR testing and 2 strata. Patients with EGFR wild type received 4 cycles of bevacizumab, pemetrexed, and cisplatin, followed by maintenance with bevacizumab and pemetrexed until progression. Patients with EGFR mutations received bevacizumab and erlotinib until progression. Patients had computed tomography scans every 6 weeks and repeat biopsy at progression. The primary end point was progression-free survival (PFS) ≥ 35% at 6 months in stratum EGFR wild type; 77 patients were required to reach a power of 90% with an alpha of 5%. Secondary end points were median PFS, overall survival, best overall response rate (ORR), and tolerability. Further biomarkers and biopsy at progression were also evaluated.
RESULTS
A total of 77 evaluable patients with EGFR wild type received an average of 9 cycles (range, 1-25). PFS at 6 months was 45.5%, median PFS was 6.9 months, overall survival was 12.1 months, and ORR was 62%. Kirsten rat sarcoma oncogene mutations and circulating vascular endothelial growth factor negatively correlated with survival, but thymidylate synthase expression did not. A total of 20 patients with EGFR mutations received an average of 16 cycles. PFS at 6 months was 70%, median PFS was 14 months, and ORR was 70%. Biopsy at progression was safe and successful in 71% of the cases.
CONCLUSIONS
Both combination therapies were promising for further studies. Biopsy at progression was feasible and will be part of future SAKK studies to investigate molecular mechanisms of resistance.
目的
旨在证明根据肿瘤组织学和表皮生长因子受体（EGFR）突变状态进行的个体化治疗以及引入新型药物联合方案治疗晚期非小细胞肺癌值得进一步研究。
方法
我们开展了一项多中心II期试验，进行强制性EGFR检测并分为2个分层。EGFR野生型患者接受4个周期的贝伐单抗、培美曲塞和顺铂治疗，随后用贝伐单抗和培美曲塞维持治疗直至病情进展。EGFR突变患者接受贝伐单抗和厄洛替尼治疗直至病情进展。患者每6周进行一次计算机断层扫描，并在病情进展时重复活检。主要终点是EGFR野生型分层中6个月时无进展生存期（PFS）≥35%；需要77例患者才能在α为5%的情况下达到90%的检验效能。次要终点是中位PFS、总生存期、最佳总体缓解率（ORR）和耐受性。还评估了进一步的生物标志物以及病情进展时的活检情况。
结果
共有77例可评估的EGFR野生型患者平均接受了9个周期的治疗（范围为1 - 25个周期）。6个月时的PFS为45.5%，中位PFS为6.9个月，总生存期为12.1个月，ORR为62%。 Kirsten大鼠肉瘤癌基因突变和循环血管内皮生长因子与生存期呈负相关，但胸苷酸合成酶表达与生存期无关。共有20例EGFR突变患者平均接受了16个周期的治疗。6个月时的PFS为70%，中位PFS为14个月，ORR为70%。71%的病例中病情进展时的活检安全且成功。
结论
两种联合治疗方案都值得进一步研究。病情进展时的活检是可行的，将成为未来瑞士癌症研究和临床肿瘤学会（SAKK）研究中探究耐药分子机制的一部分。
Zotero 插件