Abstract:
Anaplastic lymphoma kinase gene (ALK) rearrangement is present in only approximately 5% of non-small cell lung cancers (NSCLCs) and is scarce in LCNEC patients. The conventional first-line treatment options are chemotherapy combined with immunotherapy or chemotherapy followed by palliative radiotherapy. In this report, we present two cases of metastatic LCNEC with EML4-ALK fusion that were treated with ALK-TKI inhibitors and demonstrated a rapid therapeutic response. Both patients were nonsmoking women who declined cytotoxic chemotherapy, underwent Next-Generation Sequencing (NGS), and confirmed EML4-ALK fusion. They were treated with alectinib as first-line therapy, and the tumors showed significant shrinkage after two months, achieving a PR (defined as a more than 30% decrease in the sum of maximal dimensions). The PFS was 22 months and 32 months, respectively, until the last follow-up. A systematic review of all previously reported cases of LCNEC with ALK mutations identified only 21 cases. These cases were characterized by being female (71.4%), nonsmoking (85.7%), diagnosed at a relatively young age (median age 51.1), and stage IV (89.5%), with an overall response rate (ORR) of 90.5%. PFS and OS were significantly longer than those treated with conventional chemotherapy/immunotherapy. Based on the clinical characteristics and the effective therapeutic outcomes with ALK inhibitors in LCNEC patients with ALK fusion, we recommend routine ALK IHC (economical, affordable, and convenient, but with higher false positives) as a screening method in advanced LCNEC patients, particularly nonsmoking females or those who are not candidates for or unwilling to undergo cytotoxic chemotherapy. Further molecular profiling is necessary to confirm these potential beneficiaries. We suggest TKI inhibitors as the first-line treatment for metastatic LCNEC with ALK fusion. Additional studies on larger cohorts are required to assess the prevalence of ALK gene fusions and their sensitivity to various ALK inhibitors.
摘要:
间变性淋巴瘤激酶基因(ALK)重排仅存在于约5%的非小细胞肺癌(NSCLC)中,而在LCNEC患者中很少。常规的一线治疗选择是化学疗法联合免疫疗法或化学疗法,然后是姑息性放射疗法。在这份报告中,我们介绍了2例使用ALK-TKI抑制剂治疗的转移性LCNEC伴EML4-ALK融合的病例,并显示出快速的治疗反应.两名患者均为拒绝细胞毒性化疗的非吸烟女性,接受了下一代测序(NGS),并确认EML4-ALK融合。他们用阿莱替尼作为一线治疗,两个月后肿瘤明显缩小,实现PR(定义为最大尺寸总和减少30%以上)。PFS为22个月和32个月,分别,直到最后的后续行动。对所有先前报道的具有ALK突变的LCNEC病例的系统评价仅鉴定了21例。这些病例的特点是女性(71.4%),不吸烟(85.7%),诊断为相对年轻的年龄(中位年龄51.1),和第四阶段(89.5%),总有效率(ORR)为90.5%。PFS和OS明显长于常规化疗/免疫治疗。根据ALK抑制剂治疗LCNEC患者ALK融合的临床特点和疗效,我们建议常规ALKIHC(经济,负担得起的,方便,但假阳性较高)作为晚期LCNEC患者的筛查方法,特别是不吸烟的女性或不适合或不愿意接受细胞毒性化疗的女性。进一步的分子谱分析是必要的,以确认这些潜在的受益者。我们建议TKI抑制剂作为ALK融合转移性LCNEC的一线治疗。需要对更大的队列进行其他研究,以评估ALK基因融合的患病率及其对各种ALK抑制剂的敏感性。