Fournier C, Greillier L, Fina F, Secq V, Nanni-Metellus I, Loundou A, Garcia S, Ouafik L, Tomasini P, Barlesi F
Service d'oncologie multidisciplinaire et innovations thérapeutiques, Aix-Marseille université, Assistance publique-Hôpitaux de Marseille, chemin des Bourrely, 13915 Marseille cedex 20, France.
Service d'oncologie multidisciplinaire et innovations thérapeutiques, Aix-Marseille université, Assistance publique-Hôpitaux de Marseille, chemin des Bourrely, 13915 Marseille cedex 20, France; Faculté de médecine, Aix-Marseille université, Inserm U911 CRO2, 13915 Marseille, France.
Rev Mal Respir. 2016 Nov;33(9):751-756. doi: 10.1016/j.rmr.2015.12.009. Epub 2016 Mar 24.
EGFR tyrosine kinase inhibitors and crizotinib are nowadays the optimal treatment for metastatic lung cancer with activation of EGFR mutations and ALK rearrangement. In addition, several targeted agents are in development for lung cancer with other oncodrivers. In France, since 2011, six oncodrivers are routinely tested in patients with stage IV. The aim of this study was to assess whether systematic detection of oncodrivers and matched targeted therapy improve overall survival in patients with advanced lung adenocarcinoma.
This study included all consecutive patients treated in our department for advanced lung adenocarcinoma from January 2012 to December 2013. We studied the impact in survival according to the presence of the driver and the targeted therapy.
Among the 261 patients included, oncodrivers alterations were found in 43.5% of patients: EML4-ALK fusion genes (2.1%), EGFR (10.3%), KRAS (27.7%), BRAF (2.5%), HER2 (0.8%), and PI3KCA (0.8%) mutations. Twenty-nine percent of patients (n=32) with oncodrivers received matched targeted therapy. Patient treated by targeted agent appropriate to an oncogenic driver had a median survival of 21.1 months (95% CI: 14.7-27.5). The patients (n=79) who did not receive targeted therapy had a median survival of 6.6 months (95% CI: 4.3-8.9). The patients (n=150) without identified driver had a median survival of 9.7 months (95% CI: 6.7-11.7); P<0.001.
An actionable oncodriver was routinely detected in nearly half of patients with advanced lung adenocarcinoma. This systematic detection may influence treatment outcomes, notably with matched targeted therapy.
表皮生长因子受体（EGFR）酪氨酸激酶抑制剂和克唑替尼目前是治疗伴有EGFR突变激活和间变性淋巴瘤激酶（ALK）重排的转移性肺癌的最佳疗法。此外，还有几种针对具有其他致癌驱动因素的肺癌的靶向药物正在研发中。在法国，自2011年以来，六种致癌驱动因素在IV期患者中进行常规检测。本研究的目的是评估对致癌驱动因素的系统检测及相应的靶向治疗是否能提高晚期肺腺癌患者的总生存期。
本研究纳入了2012年1月至2013年12月在我科接受治疗的所有连续性晚期肺腺癌患者。我们根据是否存在驱动因素及靶向治疗情况研究其对生存的影响。
在纳入的261例患者中，43.5%的患者检测到致癌驱动因素改变：EML4-ALK融合基因（2.1%）、EGFR（10.3%）、KRAS（27.7%）、BRAF（2.5%）、HER2（0.8%）和PI3KCA（0.8%）突变。29%（n = 32）检测到致癌驱动因素的患者接受了相应的靶向治疗。接受适合致癌驱动因素的靶向药物治疗的患者中位生存期为21.1个月（95%置信区间：14.7 - 27.5）。未接受靶向治疗的患者（n = 79）中位生存期为6.6个月（95%置信区间：4.3 - 8.9）。未检测到驱动因素的患者（n = 150）中位生存期为9.7个月（95%置信区间：6.7 - 11.7）；P < 0.001。
在近一半的晚期肺腺癌患者中常规检测到可采取行动的致癌驱动因素。这种系统检测可能会影响治疗结果，尤其是通过相应的靶向治疗。
