Yan Li1, Tongtong Zhang2, Jing Zhang1, Wenbin Li1, Pei Yuan1, Puyuan Xing3, Zhou Zhang4, Shannon Chuai4, Junling Li5, Jianming Ying6. 1. Departments of Pathology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. 2. Department of Medical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen Center, Shenzhen, China. 3. Departments of Medical Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. 4. Burning Rock Biotech, Guangzhou, China. 5. Departments of Medical Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. Electronic address: drlijunling@vip.163.com. 6. Departments of Pathology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. Electronic address: jmying@cicams.ac.cn.
Abstract
INTRODUCTION: Anaplastic lymphoma kinase (ALK) rearrangements are present in approximately 5% of non-small-cell lung cancers (NSCLCs). NSCLCs with ALK-rearrangement can be effectively treated with crizotinib. However, magnitude and duration of responses are found to be heterogeneous. This study explored the clinical efficacy of crizotinib in different ALK variants. METHODS: Among 96 ALK-rearrangement patients treated with crizotinib, 60 patients were identified with tumor specimens that could be evaluated by next-generation sequencing (NGS). We retrospectively evaluated the efficacy of crizotinib in different ALK variants. RESULTS: The median Progression-free survival (PFS) of the 96 ALK-rearrangement patients was 14.17 months. Among the 60 patients with NGS results, the most frequent variants were variant 3a/b (33.33%), variant 1 (23.33%) and variant 2 (15.00%). The percentage of rare EML4-ALK variants and non EML4-ALK variants were 10.00% and 18.33%. Survival analysis showed that patients with variant 2 appeared to have longer PFS than others (P = .021); also, patients with TP53 mutation seemed to have an unfavorable PFS than those with TP53 wild-type with a borderline p value (P = .068). After adjusting for other baseline characteristics, EML4-ALK variant 2 was identified as an important factor for a better PFS of crizotinib. We also found that patients with variant 3a/b had shorter duration of response to crizotinib; however, no significant difference of PFS was observed between the PFS of variant3a/b and non-v3 EML4-ALK variants. CONCLUSIONS: Our results indicate prolonged PFS in patients with EML4-ALK variant 2.
INTRODUCTION:Anaplastic lymphoma kinase (ALK) rearrangements are present in approximately 5% of non-small-cell lung cancers (NSCLCs). NSCLCs with ALK-rearrangement can be effectively treated with crizotinib. However, magnitude and duration of responses are found to be heterogeneous. This study explored the clinical efficacy of crizotinib in different ALK variants. METHODS: Among 96 ALK-rearrangement patients treated with crizotinib, 60 patients were identified with tumor specimens that could be evaluated by next-generation sequencing (NGS). We retrospectively evaluated the efficacy of crizotinib in different ALK variants. RESULTS: The median Progression-free survival (PFS) of the 96 ALK-rearrangement patients was 14.17 months. Among the 60 patients with NGS results, the most frequent variants were variant 3a/b (33.33%), variant 1 (23.33%) and variant 2 (15.00%). The percentage of rare EML4-ALK variants and non EML4-ALK variants were 10.00% and 18.33%. Survival analysis showed that patients with variant 2 appeared to have longer PFS than others (P = .021); also, patients with TP53 mutation seemed to have an unfavorable PFS than those with TP53 wild-type with a borderline p value (P = .068). After adjusting for other baseline characteristics, EML4-ALK variant 2 was identified as an important factor for a better PFS of crizotinib. We also found that patients with variant 3a/b had shorter duration of response to crizotinib; however, no significant difference of PFS was observed between the PFS of variant3a/b and non-v3 EML4-ALK variants. CONCLUSIONS: Our results indicate prolonged PFS in patients with EML4-ALK variant 2.
Authors: Mehtap Derya Aydemirli; Jaap D H van Eendenburg; Tom van Wezel; Jan Oosting; Willem E Corver; Ellen Kapiteijn; Hans Morreau Journal: Endocr Relat Cancer Date: 2021-05-11 Impact factor: 5.678
Authors: Edyta M Urbanska; Jens B Sørensen; Linea C Melchior; Junia C Costa; Eric Santoni-Rugiu Journal: Int J Mol Sci Date: 2020-04-19 Impact factor: 5.923