Department of Breast and Medical Oncology, National Cancer Center Hospital, Tokyo, Japan.
Course of Advanced Clinical Research of Cancer, Juntendo University Graduate School of Medicine, Tokyo, Japan.
JCO Precis Oncol. 2021 May 3;5. doi: 10.1200/PO.20.00383. eCollection 2021.
Anaplastic lymphoma kinase () rearrangement is a well-known driver oncogene in non-small-cell lung cancer and has also been identified in other types of tumors. However, there is limited evidence on the clinical response to ALK tyrosine kinase inhibitors (TKIs), such as alectinib and crizotinib, in rare tumors with ALK fusion. We evaluated the therapeutic effect of ALK-TKIs in rare -rearranged tumors.
Between April 2012 and April 2019, clinical outcomes and characteristics of patients with -rearranged nonlung solid tumors who received ALK-TKIs (alectinib and/or crizotinib) outside of clinical trials were reviewed. Expression and/or rearrangement of ALK was evaluated by immunohistochemistry, fluorescence in situ hybridization, and next-generation sequencing. The tumor response was assessed according to RECIST (version 1.1). Progression-free survival was estimated from initial ALK-TKI initiation until progression.
We identified seven patients (inflammatory myofibroblastic tumors, n = 3; ALK-positive histiocytosis, n = 1; histiocytic sarcoma, n = 1; osteosarcoma, n = 1; and parotid adenocarcinoma, n = 1), with a median age of 17 years. Two rare fusions, namely, K and , were identified. As initial ALK-TKI therapy, five patients received alectinib and two received crizotinib. The objective response rate for the initial ALK-TKI therapy was 85.7% (95% CI, 44 to 97), including two patients who received alectinib and achieved complete response. The median progression-free survival was 8.1 months (range, 1.7 to not estimable). There were no treatment interruptions or dose reductions because of adverse events caused by alectinib.
This study highlights the potential benefit of ALK-TKIs, especially alectinib, in patients with -rearranged nonlung solid tumors.
间变性淋巴瘤激酶 () 重排是一种众所周知的非小细胞肺癌驱动致癌基因，也已在其他类型的肿瘤中被发现。然而，在具有 ALK 融合的罕见肿瘤中，针对 ALK 酪氨酸激酶抑制剂（TKI）（如阿来替尼和克唑替尼）的临床反应证据有限。我们评估了 ALK-TKI 在罕见的 ALK 重排肿瘤中的治疗效果。
2012 年 4 月至 2019 年 4 月，我们回顾了在临床试验之外接受 ALK-TKI（阿来替尼和/或克唑替尼）治疗的具有 - 重排的非肺部实体瘤患者的临床结果和特征。通过免疫组化、荧光原位杂交和下一代测序评估 ALK 的表达和/或重排。根据 RECIST（版本 1.1）评估肿瘤反应。无进展生存期从初始 ALK-TKI 开始到进展进行估计。
我们鉴定了 7 名患者（炎性肌纤维细胞瘤，n=3；ALK 阳性组织细胞增生症，n=1；组织细胞肉瘤，n=1；骨肉瘤，n=1；腮腺腺癌，n=1），中位年龄为 17 岁。鉴定出两种罕见的融合，即 和 。作为初始 ALK-TKI 治疗，5 名患者接受阿来替尼治疗，2 名患者接受克唑替尼治疗。初始 ALK-TKI 治疗的客观缓解率为 85.7%（95%CI，44 至 97），包括 2 名接受阿来替尼治疗并获得完全缓解的患者。中位无进展生存期为 8.1 个月（范围，1.7 至无法估计）。没有因阿来替尼引起的不良反应而中断或减少剂量。
本研究强调了 ALK-TKI，特别是阿来替尼，在具有 - 重排的非肺部实体瘤患者中的潜在获益。
