Comparative efficacy and safety of first-line treatments for advanced non-small cell lung cancer with ALK-rearranged: a meta-analysis of clinical trials

Autor: Yufeng Liu, Kailin Ding, Zhen-Zhen Xiao, Rui Zhou, Xue-Song Chang, Wen-Jie Zhao, Yi-hong Liu, Hai-Bo Zhang, Yan-juan Zhu, Ya-Dong Chen, Ya-Ya Yu, Hao-Chuan Ma
Rok vydání: 2021
Předmět:
Alectinib
Oncology
Cancer Research
medicine.medical_specialty
Lung Neoplasms
Lactams
Brigatinib
First-line treatment
Network Meta-Analysis
Population
Carbazoles
Aminopyridines
Antineoplastic Agents
Piperazines
Clinical Trials
Phase II as Topic
Organophosphorus Compounds
Piperidines
Carcinoma
Non-Small-Cell Lung
Internal medicine
Genetics
Humans
Anaplastic lymphoma kinase
Medicine
Anaplastic Lymphoma Kinase
Progression-free survival
education
Protein Kinase Inhibitors
RC254-282
Randomized Controlled Trials as Topic
Gene Rearrangement
education.field_of_study
Ceritinib
business.industry
Research
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Lorlatinib
Progression-Free Survival
Pyridazines
Clinical trial
Pyrimidines
Treatment Outcome
ALK
Clinical Trials
Phase III as Topic
Pyrazoles
Lung cancer
business
medicine.drug
Zdroj: BMC Cancer
BMC Cancer, Vol 21, Iss 1, Pp 1-11 (2021)
ISSN: 1471-2407
DOI: 10.1186/s12885-021-08977-0
Popis: Background Whereas there are many pharmacological interventions prescribed for patients with advanced anaplastic lymphoma kinase (ALK)- rearranged non-small cell lung cancer (NSCLC), comparative data between novel generation ALK-tyrosine kinase inhibitors (TKIs) remain scant. Here, we indirectly compared the efficacy and safety of first-line systemic therapeutic options used for the treatment of ALK-rearranged NSCLC. Methods We included all phase 2 and 3 randomised controlled trials (RCTs) comparing any two or three treatment options. Eligible studies reported at least one of the following outcomes: progression free survival (PFS), overall survival (OS), objective response rate (ORR), or adverse events of grade 3 or higher (Grade ≥ 3 AEs). Subgroup analysis was conducted according to central nervous system (CNS) metastases. Results A total of 9 RCTs consisting of 2484 patients with 8 treatment options were included in the systematic review. Our analysis showed that alectinib (300 mg and 600 mg), brigatinib, lorlatinib and ensartinib yielded the most favorable PFS. Whereas there was no significant OS or ORR difference among the ALK-TKIs. According to Bayesian ranking profiles, lorlatinib, alectinib 600 mg and alectinib 300 mg had the best PFS (63.7%), OS (35.9%) and ORR (37%), respectively. On the other hand, ceritinib showed the highest rate of severe adverse events (60%). Conclusion Our analysis indicated that alectinib and lorlatinib might be associated with the best therapeutic efficacy in first-line treatment for major population of advanced NSCLC patients with ALK-rearrangement. However, since there is little comparative evidence on the treatment options, there is need for relative trials to fully determine the best treatment options as well as the rapidly evolving treatment landscape.
Databáze: OpenAIRE
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