Multiple laboratory evidences indicate that distinct variants of ALK translocations differ in their biochemical properties and responsiveness to ALK tyrosine kinase inhibitors (TKIs). These data are supported by some clinical studies, which showed improved responses to crizotinib in non-small cell lung cancer (NSCLC) patients carrying particular variants of ALK translocation. We retrospectively considered 64 Russian patients with ALK-rearranged NSCLC, who were treated by crizotinib (n = 23), ceritinib (n = 39) or alectinib (n = 2). ALK fusion variants were genotyped by PCR. Median progression-free survival (PFS) approached to 18 and 21 months in subjects with “short” (v.3a/b, v.5a/b) vs. “long” (TAPE-domain containing) fusion variants (p = 0.783), respectively; similar data were obtained while comparing EML4/ALK variant 1 vs. other ALK translocations (19 and 21 months, respectively; p = 0.604). Objective response rates were also strikingly similar in the above groups (“short”: 88%, “long”: 77%, p = 0.479; variant 1: 76%, other translocations: 81%, p = 0.753). Furthermore, ALK variants did not influence the disease outcomes when patients treated by crizotinib and ceritinib were analyzed separately. Overall, PFS on ALK TKI did not depend on whether the drug was administered upfront or after chemotherapy. Ceritinib produced significantly longer PFS than crizotinib (p = 0.022). In conclusion, this study revealed that distinct ALK translocation variants render similar clinical responsiveness to ALK inhibitors.

多个实验室证据表明，ALK易位的不同变体在其生化特性和对ALK酪氨酸激酶抑制剂（TKIs）的响应性方面有所不同。这些数据得到了一些临床研究的支持，这些研究表明，在携带ALK易位变体的非小细胞肺癌（NSCLC）患者中，对克唑替尼的反应有所改善。我们回顾性分析了64例ALK重排NSCLC的俄罗斯患者，这些患者接受了crizotinib（n = 23），ceritinib（n = 39）或alectinib（n = 2）的治疗。通过PCR对ALK融合变体进行基因分型。具有“短”（v.3a / b，v.5a / b）与“长”（包含TAPE域）融合变体（p = 0.783）的受试者的中位无进展生存期（PFS）接近18和21个月）， 分别; 比较EML4 / ALK变体1与EML4 / ALK变体时获得了相似的数据。其他ALK易位（分别为19和21个月； p = 0.604）。在上述组中，客观缓解率也非常相似（“短”：88％，“长”：77％，p = 0.479；变体1：76％，其他易位：81％，p = 0.753）。此外，当分别对克唑替尼和赛立替尼治疗的患者进行分析时，ALK变异体不会影响疾病的预后。总体而言，ALK TKI上的PFS并不取决于药物是预先给药还是在化疗后给药。Ceritinib产生的PFS比crizotinib长得多（p = 0.022）。总之，这项研究表明，不同的ALK易位变体对ALK抑制剂的临床反应相似。变体1：76％，其他易位：81％，p = 0.753）。此外，当分别对克唑替尼和赛立替尼治疗的患者进行分析时，ALK变异体不会影响疾病的预后。总体而言，ALK TKI上的PFS并不取决于药物是预先给药还是在化疗后给药。Ceritinib产生的PFS比crizotinib长得多（p = 0.022）。总之，这项研究表明，不同的ALK易位变体对ALK抑制剂的临床反应相似。变体1：76％，其他易位：81％，p = 0.753）。此外，当分别对克唑替尼和赛立替尼治疗的患者进行分析时，ALK变异体不会影响疾病的预后。总体而言，ALK TKI上的PFS并不取决于药物是预先给药还是在化疗后给药。Ceritinib产生的PFS比crizotinib长得多（p = 0.022）。总之，这项研究表明，不同的ALK易位变体对ALK抑制剂的临床反应相似。Ceritinib产生的PFS比crizotinib长得多（p = 0.022）。总之，这项研究表明，不同的ALK易位变体对ALK抑制剂的临床反应相似。Ceritinib产生的PFS比crizotinib长得多（p = 0.022）。总之，这项研究表明，不同的ALK易位变体对ALK抑制剂的临床反应相似。