Department of Medical Oncology, Lung Cancer and Gastrointestinal Unit, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, People's Republic of China.
Department of Medical Oncology, Second Chest Cancer Unit, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Changsha, People's Republic of China.
J Thorac Oncol. 2020 Jun;15(6):1027-1036. doi: 10.1016/j.jtho.2020.02.007. Epub 2020 Feb 27.
During nonreciprocal/reciprocal translocation process, 5'-anaplastic lymphoma kinase (ALK) sometimes gets retained in the genome and is detectable by next-generation sequencing; however, no study has investigated its clinical significance. Our study aimed to assess the impact of harboring 5'-ALK on the efficacy of crizotinib.
A total of 150 patients with next-generation sequencing-identified ALK-rearranged NSCLC from March 2014 to July 2018 at the Hunan Cancer Hospital were enrolled in this study. The efficacy of crizotinib as first-line therapy was evaluated in 112 patients according to the retention of 5'-ALK.
Among the 150 patients with NSCLC, nonreciprocal/reciprocal translocation was detected in 18.7% (28 of 150), and 3'-ALK fusion alone was detected in 81.3% (122 of 150). Among the 112 patients who received first-line crizotinib, 89 had 3'-ALK fusion alone (79 echinoderm microtubule associated protein-like 4 [EML4]-ALK and 10 non-EML4-ALK), and 23 had nonreciprocal/reciprocal ALK translocation. Among the patients with nonreciprocal/reciprocal ALK translocation, three patients harbored dual concurrent 3'-ALK fusions. Patients with nonreciprocal/reciprocal ALK translocation had higher incidence of brain metastasis at baseline than those with 3'-ALK fusion alone (39.1% versus 13.4%, p = 0.028). Crizotinib-treated patients with nonreciprocal/reciprocal ALK translocation had significantly shorter median progression-free survival (PFS) compared with patients carrying 3'-ALK fusion alone (6.1 m versus 12.0 m, p = 0.001) or with EML4-ALK fusion alone (6.1 m versus 12.6 m, p = 0.001). Multivariate analysis revealed that harboring nonreciprocal/reciprocal ALK translocation was an independent predictor of worse PFS for crizotinib-treated ALK-rearranged NSCLC (p = 0.0046).
Presence of nonreciprocal/reciprocal ALK translocation was predictive for worse PFS and greater likelihood of baseline brain metastases in patients with ALK-rearranged NSCLC who received first-line crizotinib.
在非相互/相互易位过程中，5'-间变性淋巴瘤激酶（ALK）有时会保留在基因组中，并可通过下一代测序检测到；然而，尚无研究探讨其临床意义。我们的研究旨在评估携带 5'-ALK 对克唑替尼疗效的影响。
本研究纳入了 2014 年 3 月至 2018 年 7 月在湖南省肿瘤医院接受下一代测序确定的 ALK 重排非小细胞肺癌（NSCLC）的 150 例患者。根据 5'-ALK 的保留情况，评估 112 例患者接受克唑替尼一线治疗的疗效。
在 150 例 NSCLC 患者中，检测到非相互/相互易位占 18.7%（28/150），3'-ALK 融合单独检测占 81.3%（122/150）。在接受一线克唑替尼治疗的 112 例患者中，89 例仅存在 3'-ALK 融合（79 例棘皮动物微管相关蛋白样 4 [EML4]-ALK 和 10 例非 EML4-ALK），23 例存在非相互/相互 ALK 易位。在存在非相互/相互 ALK 易位的患者中，有 3 例患者同时存在双 3'-ALK 融合。与仅存在 3'-ALK 融合的患者相比，存在非相互/相互 ALK 易位的患者基线时脑转移的发生率更高（39.1%比 13.4%，p=0.028）。与仅携带 3'-ALK 融合的患者（6.1 个月比 12.0 个月，p=0.001）或仅携带 EML4-ALK 融合的患者（6.1 个月比 12.6 个月，p=0.001）相比，接受非相互/相互 ALK 易位治疗的克唑替尼治疗患者的中位无进展生存期（PFS）明显更短。多因素分析显示，携带非相互/相互 ALK 易位是接受克唑替尼治疗的 ALK 重排 NSCLC 患者 PFS 更差的独立预测因素（p=0.0046）。
在接受一线克唑替尼治疗的 ALK 重排 NSCLC 患者中，存在非相互/相互 ALK 易位与 PFS 更差和更大的基线脑转移可能性相关。
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