Medical Oncology Unit, University Hospital of Parma, Parma, Italy.
Medical Oncology Unit, University Hospital of Parma, Parma, Italy.
Clin Lung Cancer. 2018 Mar;19(2):e151-e161. doi: 10.1016/j.cllc.2017.10.008. Epub 2017 Oct 28.
Lung toxicity is a potential fatal effect involving non-small-cell lung cancer (NSCLC) patients exposed to tyrosine kinase inhibitors (TKIs). Moving from our experience regarding a patient who developed lung toxicity while receiving 2 different anaplastic lymphoma kinase (ALK)-TKIs, we performed a systematic review to assess the epidemiologic magnitude and the clinical significance of such toxicity in NSCLC patients treated with ALK-TKIs. Studies were identified using MEDLINE and additional sources (European Society for Medical Oncology, American Society of Clinical Oncology, and World Conference on Lung Cancer abstracts) in agreement with Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Cochrane guidelines. Lung toxicity was reported in 105 of 4943 NSCLC patients (2.1%). Crizotinib was responsible for pulmonary adverse events (AEs) in 1.8% of exposed patients (49 of 2706). With the limit of a lower number of treated patients (n = 359), brigatinib resulted as the most frequently involved in lung toxicity (7%; n = 25). Pulmonary AEs during therapy with ceritinib, alectinib, and lorlatinib occurred in 1.1%, 2.6%, and 1.8% of the patients, respectively. Sixty-five percent of cases accounted for Grade 3 or 4 events, with a mortality rate of 9%. Radiological patterns of pneumonia were reported in 25 patients, whereas imaging evocative of interstitial lung disease in 37. Overall, 26 of 105 patients (25%) permanently discontinued treatment because of lung toxicity. Lung toxicity is a rare albeit potentially severe side effect in NSCLC patients receiving ALK-TKIs, apparently more frequent with brigatinib. Its early recognition and treatment are crucial for the best outcome of this subgroup of patients, whose overall prognosis is being improved by the availability of several targeted agents.
肺毒性是一种潜在的致命效应，涉及接受酪氨酸激酶抑制剂（TKI）的非小细胞肺癌（NSCLC）患者。根据我们在接受 2 种不同间变性淋巴瘤激酶（ALK）-TKI 治疗的患者中发生肺毒性的经验，我们进行了一项系统评价，以评估接受 ALK-TKI 治疗的 NSCLC 患者发生这种毒性的流行病学程度和临床意义。使用 MEDLINE 和其他来源（欧洲肿瘤内科学会、美国临床肿瘤学会和世界肺癌大会摘要），根据系统评价和荟萃分析的首选报告项目以及 Cochrane 指南，确定了研究。在 4943 例 NSCLC 患者中，有 105 例（2.1%）报告了肺毒性。在暴露于克唑替尼的患者中，有 1.8%（49 例）发生了肺部不良事件（AE）。由于治疗患者数量较少（n=359），brigatinib 是最常涉及肺毒性的药物（7%；n=25）。在接受 ceritinib、alectinib 和 lorlatinib 治疗期间，肺毒性分别发生在 1.1%、2.6%和 1.8%的患者中。65%的病例为 3 级或 4 级事件，死亡率为 9%。25 例患者报告了肺炎的放射学模式，37 例患者报告了间质性肺疾病的影像学表现。总体而言，由于肺毒性，105 例患者中有 26 例（25%）永久停止治疗。肺毒性是接受 ALK-TKI 的 NSCLC 患者罕见但潜在严重的副作用，brigatinib 似乎更常见。早期识别和治疗对于这组患者的最佳结局至关重要，由于多种靶向药物的出现，这些患者的总体预后正在得到改善。
