Medical Oncology Department, Gustave Roussy, Villejuif, France.
Medical Oncology Department, Gustave Roussy, Villejuif, France; Cancer Medicine Department, University Paris-Saclay, Orsay, France.
J Thorac Oncol. 2018 Mar;13(3):301-322. doi: 10.1016/j.jtho.2018.01.002. Epub 2018 Jan 11.
The treatment paradigm of NSCLC underwent a major revolution during the course of 2017. Immune checkpoint inhibitors (ICIs) brought remarkable improvements in response and overall survival both in unselected pretreated patients and in untreated patients with programmed death ligand 1 expression of 50% or more. Furthermore, compelling preliminary results were reported for new combinations of anti-programmed cell death 1/programmed death ligand 1 agents with chemotherapy or anti-cytotoxic T-lymphocyte associated protein 4 inhibitors. The success of the ICIs appeared to extend to patients with SCLC, mesothelioma, or thymic tumors. Furthermore, in SCLC, encouraging activity was reported for an experimental target therapy (rovalpituzumab teserine) and a new chemotherapeutic agent (lurbinectedin). For oncogene-addicted NSCLC, next-generation tyrosine kinase inhibitors (TKIs) (such as osimertinib or alectinib) have demonstrated increased response rates and progression-free survival compared with first-generation TKIs in patients with both EGFR-mutated and ALK receptor tyrosine kinase gene (ALK)-rearranged NSCLC. However, because of the lack of mature overall survival data and considering the high efficacy of these drugs in patients with NSCLC previously exposed to first- or second-generation TKIs, definitive conclusions concerning the best treatment sequence cannot yet be drawn. In addition, new oncogenes such as mutant BRAF, tyrosine-protein kinase met gene (MET) and erb-b2 receptor tyrosine kinase 2 gene (HER2), and ret proto-oncogene (RET) rearrangements have joined the list of potential targetable drivers. In conclusion, the field of thoracic oncology is on the verge of a breakthrough that will open up many promising new therapeutic options for physicians and patients. The characterization of biomarkers predictive of sensitivity or resistance to immunotherapy and the identification of the optimal therapeutic combinations (for ICIs) and treatment sequence (for oncogene-addicted NSCLC) represent the toughest upcoming challenges in the domain of thoracic oncology.
2017 年期间，非小细胞肺癌（NSCLC）的治疗模式发生了重大变革。免疫检查点抑制剂（ICI）在未经选择的预处理患者和程序性死亡配体 1 表达为 50%或更高的未经治疗患者中，均显著提高了反应率和总生存率。此外，新的抗程序性死亡 1/程序性死亡配体 1 药物与化疗或抗细胞毒性 T 淋巴细胞相关蛋白 4 抑制剂联合应用的初步结果也令人信服。ICI 的成功似乎扩展到了小细胞肺癌（SCLC）、间皮瘤或胸腺瘤患者。此外，在 SCLC 中，实验性靶向治疗（rovalpituzumab teserine）和新型化疗药物（lurbinectedin）也显示出了令人鼓舞的活性。对于致癌基因依赖性 NSCLC，与第一代酪氨酸激酶抑制剂（TKI）相比，下一代酪氨酸激酶抑制剂（TKI）（如奥希替尼或阿来替尼）在 EGFR 突变和 ALK 受体酪氨酸激酶基因（ALK）重排的 NSCLC 患者中，提高了反应率和无进展生存期。然而，由于缺乏成熟的总生存期数据，并且考虑到这些药物在先前接受过第一代或第二代 TKI 治疗的 NSCLC 患者中的高疗效，目前还不能确定最佳治疗顺序。此外，新的致癌基因，如突变型 BRAF、酪氨酸蛋白激酶 met 基因（MET）和 erb-b2 受体酪氨酸激酶 2 基因（HER2）以及 ret 原癌基因（RET）重排，已加入潜在可靶向驱动基因之列。总之，胸部肿瘤学领域即将取得突破，这将为医生和患者开辟许多有前途的新治疗选择。免疫治疗敏感性或耐药性的生物标志物的特征以及最佳治疗组合（ICI）和治疗顺序（致癌基因依赖性 NSCLC）的确定，代表了胸部肿瘤学领域最具挑战性的未来挑战。
