Analysis of Baseline Molecular Factors Associated With the Risk of Central Nervous System Progression Among Alectinib-Treated Patients With ALK–Positive NSCLC

Lianxi Song, MD; Huan Yan, MD; Qinqin Xu, MD; Chunhua Zhou, MD; Juan Liang, MD; Shaoding Lin, MD; Ruiguang Zhang, MD; Juan Yu, MD; Yang Xia, MD; Nong Yang, MD; Liang Zeng, MD; Yongchang Zhang, MD

JTO Clinical and Research Reports (Dec 2024)

Analysis of Baseline Molecular Factors Associated With the Risk of Central Nervous System Progression Among Alectinib-Treated Patients With ALK–Positive NSCLC

Lianxi Song, MD,
Huan Yan, MD,
Qinqin Xu, MD,
Chunhua Zhou, MD,
Juan Liang, MD,
Shaoding Lin, MD,
Ruiguang Zhang, MD,
Juan Yu, MD,
Yang Xia, MD,
Nong Yang, MD,
Liang Zeng, MD,
Yongchang Zhang, MD

Affiliations

Lianxi Song, MD: Department of Medical Oncology, Lung Cancer and Gastrointestinal Unit, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, People's Republic of China; Graduate Collaborative Training Base of Hunan Cancer Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, People's Republic of China; Department of Medical Oncology, Yiyang Center Hospital, Yiyang, People's Republic of China
Huan Yan, MD: Department of Medical Oncology, Lung Cancer and Gastrointestinal Unit, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, People's Republic of China; Graduate Collaborative Training Base of Hunan Cancer Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, People's Republic of China
Qinqin Xu, MD: Department of Medical Oncology, Qinghai Provincial People's Hospital, Xining, People's Republic of China
Chunhua Zhou, MD: Department of Medical Oncology, Lung Cancer and Gastrointestinal Unit, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, People's Republic of China
Juan Liang, MD: Department of Medical Oncology, Yiyang Center Hospital, Yiyang, People's Republic of China
Shaoding Lin, MD: Department of Medical Oncology, The First Affiliated Hospital of Hunan University of Medicine, Huaihua, People's Republic of China
Ruiguang Zhang, MD: Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China
Juan Yu, MD: Department of Medical Oncology, Zhangjiajie People’s Hospital, Zhangjiajie, Hunan, People's Republic of China
Yang Xia, MD: Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People's Republic of China
Nong Yang, MD: Department of Medical Oncology, Lung Cancer and Gastrointestinal Unit, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, People's Republic of China; Graduate Collaborative Training Base of Hunan Cancer Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, People's Republic of China
Liang Zeng, MD: Department of Medical Oncology, Lung Cancer and Gastrointestinal Unit, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, People's Republic of China
Yongchang Zhang, MD: Department of Medical Oncology, Lung Cancer and Gastrointestinal Unit, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, People's Republic of China; Graduate Collaborative Training Base of Hunan Cancer Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, People's Republic of China; Faculty of Furong Laboratory, Changsha, People's Republic of China; Corresponding author. Address for correspondence: Yongchang Zhang, MD, Department of Medical Oncology, Lung Cancer and Gastrointestinal Unit, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, NO. 283 Tongzipo Road, Changsha 410001, People's Republic of China.

Journal volume & issue: Vol. 5, no. 12
p. 100729

Abstract

Read online

Introduction: Despite receiving alectinib therapy, patients with ALK-positive NSCLC remain at risk of central nervous system (CNS) progression. Our retrospective study aimed to identify baseline clinical and molecular factors associated with the risk of CNS progression in this patient subset. Methods: We analyzed the clinical, molecular, and imaging data of 318 patients with ALK-positive advanced NSCLC who received alectinib as first-line (1L-alectinib) or second-line (2L-alectinib) therapy at baseline (1L, n = 183; 2L, n = 135) and at disease progression (1L, n = 80; 2L, n = 76). Results: The incidence rates of CNS progression were 23.7% after 1L-alectinib treatment and 31.6% after 2L-alectinib treatment. Compared with patients who received 1L-alectinib, CNS progression was similar in patients who received 2L-alectinib (p > 0.05). Oligoprogression was detected in 55.0% (44 of 80) of patients who progressed after first-line alectinib, with the remaining 45.0% (36 of 80) having nonoligoprogression. Univariate and multivariate analyses and stepwise regression analyses consistently identified a higher likelihood of CNS progression among (1) patients who received 2L-alectinib than 1L-alectinib, (2) patients with non-3a/b variant ALK fusion than those with echinoderm microtubule-associated protein-like 4–ALK variant 3a/b, and (3) patients with programmed death ligand 1 (PD-L1) tumor proportion score (TPS) of 50% or higher than PD-L1 TPS of less than 50%. Conclusions: Our study provided real-world evidence that patients who harbored PD-L1 TPS of 50% or higher were more likely to experience CNS progression during alectinib therapy. The association between CNS progression and breakpoint variants warrants further investigation. Our findings suggest that close monitoring and prompt intervention are crucial in prolonging the quality of life of this patient subset.

Published in JTO Clinical and Research Reports

ISSN: 2666-3643 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Website: https://www.journals.elsevier.com/jto-clinical-and-research-reports/

About the journal

Abstract

Keywords