Respiratory Center, Matsusaka Municipal Hospital, 1550 Tonomachi, Matsusaka City, Mie, 515-0073, Japan.
Department of Biostatistics, Yokohama City University School of Medicine, 22-2 Seto, Kanazawa-ku, Yokohama, Kanagawa, 236-0027, Japan.
Eur J Cancer. 2021 Mar;145:183-193. doi: 10.1016/j.ejca.2020.12.026. Epub 2021 Jan 22.
The data of sequential therapy of anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) in clinical practice have been limited.
We reviewed the clinical data of patients with ALK-rearranged non-small cell lung cancer who received crizotinib (CRZ) or alectinib (ALEC) between May 2012 and December 2016. Patients were divided into two groups based on the first-administered ALK-TKI, the CRZ or ALEC group. The combined time-to-treatment failure (TTF) was defined as the sum of the 'TTF of CRZ' plus the 'TTF of ALEC' if patients were treated with CRZ followed by ALEC in the CRZ group. The primary end-point is the comparison between the combined TTF and the TTF of ALEC in the ALEC group.
Of 864 patients enrolled from 61 institutions, 840 patients were analysed. There were 535 of 305 patients in the CRZ/ALEC groups. The combined TTF in the CRZ group was significantly longer than TTF in the ALEC group (median, 34.4 versus 27.2 months; hazard ratio [HR], 0.709; P = 0.0044). However, there was no significant difference in overall survival (OS) between the patients who received ALEC after CRZ in the CRZ group and the patients in the ALEC group (median, 88.4 months versus. not reached; HR, 1.048; P = 0.7770). In the whole population, the CRZ group had a significantly shorter OS than the ALEC group (median, 53.6 months versus not reached; HR, 1.821, P < 0.0001).
The combined TTF in the CRZ group was significantly longer than the TTF in the ALEC group; however, OS benefit of sequential therapy against ALEC as the first ALK-TKI was not shown.
临床实践中,间变性淋巴瘤激酶(ALK)酪氨酸激酶抑制剂(TKI)序贯治疗的数据有限。
我们回顾了 2012 年 5 月至 2016 年 12 月期间接受克唑替尼(CRZ)或阿来替尼(ALEC)治疗的 ALK 重排非小细胞肺癌患者的临床数据。根据首次使用的 ALK-TKI,将患者分为 CRZ 或 ALEC 组。如果 CRZ 组患者先接受 CRZ 治疗,然后再接受 ALEC 治疗,则联合治疗失败时间(TTF)定义为“CRZ 的 TTF 之和+ALEC 的 TTF”。主要终点是比较 CRZ 组的联合 TTF 与 ALEC 组的 ALEC TTF。
在 61 家机构纳入的 864 名患者中,有 840 名患者纳入分析。CRZ/ALEC 组中,305 名患者中有 535 名患者。CRZ 组的联合 TTF 明显长于 ALEC 组(中位时间:34.4 个月比 27.2 个月;风险比 [HR],0.709;P=0.0044)。然而,CRZ 组中先接受 CRZ 治疗后再接受 ALEC 治疗的患者与 ALEC 组患者的总生存(OS)无显著差异(中位时间:88.4 个月比未达到;HR,1.048;P=0.7770)。在全人群中,CRZ 组的 OS 明显短于 ALEC 组(中位时间:53.6 个月比未达到;HR,1.821,P<0.0001)。
CRZ 组的联合 TTF 明显长于 ALEC 组,但序贯治疗相对于作为一线 ALK-TKI 的 ALEC 并未显示出 OS 获益。