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Multicenter Study
. 2022 Jan;13(1):107-116.
doi: 10.1111/1759-7714.14232. Epub 2021 Dec 1.

Clinical outcome, long-term survival and tolerability of sequential therapy of first-line crizotinib followed by alectinib in advanced ALK+NSCLC: A multicenter retrospective analysis in China

Zihua Zou  1 , Xuezhi Hao  1 , Cuiying Zhang  2 , Haojing Li  2 , Guilan Dong  3 , Yumei Peng  3 , Kewei Ma  4 , Ye Guo  4 , Li Shan  5 , Yan Zhang  5 , Li Liang  6 , Yangchun Gu  6 , Puyuan Xing  1 , Junling Li  1
Affiliations
Multicenter Study

Clinical outcome, long-term survival and tolerability of sequential therapy of first-line crizotinib followed by alectinib in advanced ALK+NSCLC: A multicenter retrospective analysis in China

Zihua Zou et al. Thorac Cancer. 2022 Jan.

Abstract

Background: There is limited data on the clinical outcome, long-term survival and tolerability of sequential therapy of first-line crizotinib followed by alectinib in a real-world setting for Chinese patients with advanced ALK+ NSCLC.

Methods: The medical records of patients who received sequential therapy with first-line crizotinib followed by alectinib (no intermittent systemic therapy was allowed between the two ALK-TKIs) were collected from six centers in China. Combined time treatment to failure (C-TTF) was defined as the period from the start of crizotinib to the complete discontinuation of alectinib due to any cause.

Results: A total of 61 patients were included in our study. Fifty-two patients were switched to alectinib due to disease progression, seven as a result of toxicity, and two due to patient preference. At the time of data cutoff, alectinib treatment was discontinued in 31 patients on account of disease progression while severe adverse events resulted in cessation of alectinib in another two patients. Rebiopsy was conducted in 21 patients following disease progression on alectinib in whom ALK secondary mutation was found in 13 patients. Patients with ALK secondary mutation demonstrated better PFS during treatment with subsequent ALK-TKIs compared with those without (10.4 vs. 3.1 m, p = 0.0018, HR = 0.08). With a median follow-up of 34.3 months, C-TTF was 39.2 months and estimated 5-year OS was 68.6% in the overall population.

Conclusion: Sequential therapy with first-line crizotinib followed by alectinib demonstrated long-term benefits. Different efficacy in subsequent ALK-TKI between patients with or without ALK secondary mutation further emphasized the importance of rebiopsy to guide targeted therapy more precisely.

Keywords: ALK+ NSCLC; Alectinib; Crizotinib.

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Conflict of interest statement

No authors report any conflict of interest.

Figures

FIGURE 1
FIGURE 1
(a) Waterfall plots for patients with target lesions during treatment with crizotinib (n = 42). (b) Extent of tumor reduction during treatment with crizotinib (n = 42). (c) Waterfall plots for patients with target lesions during treatment with alectinib. (d) Extent of tumor reduction during treatment with alecitnib (n = 46)
FIGURE 2
FIGURE 2
(a) Progression‐free survival during treatment with crizotinib in crizotinib‐resistant patients (n = 52). (b) Time to treatment failure during treatment with crizotinib in the overall population (n = 61). (c) Progression‐free survival during treatment with alectinib in crizotinib‐resistant patients (n = 52). (d) CNS time to progression during treatment with alectinib in crizotinib‐resistant patients (n = 35)
FIGURE 3
FIGURE 3
(a) Overall survival in crizotinib‐resistant patients (n = 52). (b) Overall survival in overall population (n = 61). (c) Time to treatment failure during treatment with crizotinib to alectinib in the overall population (n = 61)
FIGURE 4
FIGURE 4
(a) ALK secondary mutation following disease progression on alectinib. (b) Progression‐free survival during the treatment of subsequent ALK‐TKI between patients with or without secondary ALK mutation
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