Author:
Ma Hao-chuan,Liu Yi-hong,Ding Kai-lin,Liu Yu-feng,Zhao Wen-jie,Zhu Yan-juan,Chang Xue-song,Chen Ya-dong,Xiao Zhen-zhen,Yu Ya-ya,Zhou Rui,Zhang Hai-bo
Abstract
Abstract
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.
Publisher
Springer Science and Business Media LLC
Subject
Cancer Research,Genetics,Oncology
Reference54 articles.
1. Sung H, Ferlay J, Siegel R, Laversanne M, Soerjomataram I, Jemal A, Bray FJCacjfc: Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. 2021, 71(3):209–249.
2. Zappa C, Mousa SAJTlcr: Non-small cell lung cancer: current treatment and future advances. 2016, 5(3):288.
3. Shaw AT, Yeap BY, Mino-Kenudson M, Digumarthy SR, Costa DB, Heist RS, Solomon B, Stubbs H, Admane S, McDermott UJJoco: Clinical features and outcome of patients with non–small-cell lung cancer who harbor EML4-ALK. 2009, 27(26):4247.
4. Shaw AT, Engelman JAJJoco: ALK in lung cancer: past, present, and future. 2013, 31(8):1105.
5. Kim H, Chung JJTlcr: Overview of clinicopathologic features of ALK-rearranged lung adenocarcinoma and current diagnostic testing for ALK rearrangement. 2015, 4(2):149–155.