Highlights
- •Large-scale real-world data showed longer progression-free survival of alectinib than crizotinib.
- •But, propensity score analysis of overall survival could not show the superiority of alectinib.
- •Poor responders to crizotinib had poorer response also to alectinib.
- •Ceritinib or lorlatinib showed activity even after crizotinib or alectinib therapy.
- •Meanwhile, immunotherapy could not show clinical benefit in our data.
Abstract
Background
The data of sequential therapy of anaplastic lymphoma kinase (ALK) tyrosine kinase
inhibitors (TKIs) in clinical practice have been limited.
Methods
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.
Results
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).
Conclusion
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.
Keywords
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Article info
Publication history
Published online: January 21, 2021
Accepted:
December 20,
2020
Received in revised form:
December 15,
2020
Received:
October 7,
2020
Identification
Copyright
© 2021 Elsevier Ltd. All rights reserved.
