Advanced Squamous Cell Carcinoma of the Lung: Current Treatment Approaches and the Role of Afatinib.
Advanced Squamous Cell Carcinoma of the Lung: Current Treatment Approaches and the Role of Afatinib.
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DOI：
10.2147/ott.s250446
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发表时间：
2020
影响因子：
4
通讯作者：
Hart L
中科院分区：
文献类型：
--
作者：
Santos ES;Hart L
近年来，随着免疫检查点抑制剂在一线和二线环境中的常规临床实践中的引入，鳞状细胞肺癌的治疗选择有所扩大，但仍然有限。因此，pembrolizumab，无论是单独使用还是与铂类化疗联合使用，现在都是鳞状细胞肺癌的标准一线治疗。然而，一旦患者在免疫检查点抑制剂和化疗方面取得进展，几乎没有选择。在这种情况下，不可逆的ErbB家族阻滞剂阿法替尼可能作为某些患者的第二种或后续治疗。III期LUX-Lung 8研究表明，在鳞状细胞肺癌患者中，与厄洛替尼相比，阿法替尼显著延长了无进展生存期和总生存期。值得注意的是，对LUX-Lung 8患者子集的回顾性、特别生物标志物分析表明，ErbB家族突变患者从阿法替尼中获益特别大，尤其是ErbB 2（HER 2）突变患者。阿法替尼具有可管理和可预测的安全性特征，不良事件可通过使用耐受性指导的剂量调整方案进行管理。在获得更多数据之前，阿法替尼可被视为帕博利珠单抗和含铂化疗联合治疗后发生进展且不适合接受更成熟二线治疗的患者的潜在二线治疗选择，或接受一线免疫治疗和二线化疗或化疗和抗血管生成治疗的患者的三线治疗选择。然而，需要进一步的数据来支持免疫治疗后使用阿法替尼。鉴于在这两种情况下治疗选择都是有限的，因此有必要研究具有全新作用机制的药物。如果可用，通过分子分析确定ErbB家族突变或使用蛋白质组学分析可能有助于进一步分离可能从阿法替尼中获益最多的患者。
Options for the treatment of squamous cell lung carcinoma expanded in recent years with the introduction of the immune checkpoint inhibitors into routine clinical practice in both the first- and second-line settings but are still limited. As a result, pembrolizumab, given either alone or in combination with platinum-based chemotherapy, is now a standard first-line treatment for squamous cell lung cancer. However, few options exist once patients have progressed on immune checkpoint inhibitors and chemotherapy. In this setting, the irreversible ErbB family blocker, afatinib, has a potential role as second or subsequent therapy for some patients. The Phase III LUX-Lung 8 study demonstrated that afatinib significantly prolonged progression-free and overall survival compared with erlotinib in patients with squamous cell lung carcinoma. Notably, retrospective, ad-hoc biomarker analyses of a subset of patients from LUX-Lung 8 suggested that patients with ErbB family mutations derived particular benefit from afatinib, especially those with ErbB2 (HER2) mutations. Afatinib has a manageable and predictable safety profile, and adverse events can be managed with the use of a tolerability-guided dose modification protocol. Until more data are available, afatinib could be considered as a potential second-line treatment option for patients who have progressed on combined pembrolizumab and platinum-based chemotherapy and are ineligible for more established second-line options, or as a third-line option in patients who have received first-line immunotherapy, and second-line chemotherapy or chemotherapy and antiangiogenesis therapy. However, further data are required to support the use of afatinib following immunotherapy. Given that treatment options are limited in both of these settings, investigating an agent with an entirely new mechanism of action is warranted. If available, molecular analysis to identify ErbB family mutations or the use of proteomic profiling could help to further isolate patients who are likely to derive the most benefit from afatinib.