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Progress in the Management of Advanced Thoracic Malignancies in 2017
Journal of Thoracic Oncology ( IF 20.4 ) Pub Date : 2018-03-01 , DOI: 10.1016/j.jtho.2018.01.002
Roberto Ferrara , Laura Mezquita , Benjamin Besse

ABSTRACT 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.

中文翻译:

2017年晚期胸部恶性肿瘤管理进展

摘要 NSCLC 的治疗范式在 2017 年期间发生了重大变革。免疫检查点抑制剂 (ICIs) 在未经选择的预处理患者和未经治疗的程序性死亡配体 1 表达 50% 或更高的患者中带来了显着改善的反应和总生存期. 此外,抗程序性细胞死亡 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 抑制剂的新组合报告了令人信服的初步结果。ICI 的成功似乎扩展到了 SCLC、间皮瘤或胸腺肿瘤患者。此外,在 SCLC 中,实验性靶点治疗(rovalpituzumab teserine)和新的化疗药物(lurbinectedin)的活性令人鼓舞。对于癌基因成瘾的非小细胞肺癌,与第一代 TKI 相比,下一代酪氨酸激酶抑制剂 (TKIs)(如奥希替尼或艾乐替尼)在 EGFR 突变和 ALK 受体酪氨酸激酶基因 (ALK) 重排的患者中显示出更高的反应率和无进展生存期非小细胞肺癌。然而,由于缺乏成熟的总生存数据,并考虑到这些药物对先前暴露于第一代或第二代 TKI 的 NSCLC 患者的高疗效,尚无法得出关于最佳治疗顺序的明确结论。此外,突变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)重排等新致癌基因也加入了潜在的可靶向驱动因素列表。综上所述,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希望的新治疗选择。预测免疫治疗敏感性或耐药性的生物标志物的表征以及最佳治疗组合(针对 ICI)和治疗顺序(针对致癌基因成瘾的 NSCLC)的确定代表了胸部肿瘤学领域即将面临的最艰巨的挑战。
更新日期:2018-03-01
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