Crizotinib Versus Conventional Chemotherapy in First-Line Treatment for ALK-Positive Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis

Abstract

Introduction: Lung cancer is the most frequently diagnosed type of cancer and the main cause of death from malignant neoplasms worldwide. One of the most recent discoveries in the context of non-small cell lung cancer (NSCLC) was the mutation of the anaplastic lymphoma kinase receptor (ALK). This genetic alteration is found in approximately 2-5% of NSCLC patients, and crizotinib was the first targeted therapy discovered for its first-line treatment.Objective: To conduct a systematic review and meta-analysis to estimate the magnitude of the overall survival (OS) and progression-free survival (PFS) from using crizotinib as treatment compared to traditional chemotherapy to guide future decision making. Methods: PRISMA and Cochrane recommendations were followed using the findings based on studies published in the main international electronic databases. Selection criteria included the following: randomized clinical trials (RCT) or cohort studies that had assessed the efficacy and effectiveness of crizotinib as monotherapy in patients with NSCLC with ALK fusions. Results: From 2504 publications identified in the literature, only eight publications referring to seven studies met the selection criteria, with high heterogeneity identified between the studies. Overall, there was a significant gain in PFS (HR 0.38; 95% CI 0.30-0.49; p \ 0.00001); however, there was no significant gain in OS (HR 0.68; 95% CI 0.43-1.08; p = 0.10). Conclusion:The study highlighted and confirmed that treatment with crizotinib led to clinical improvement in PFS among patients with advanced NSCLC with ALK fusion, as previously reported. However, there was no increase in overall survival in patients with NSCLC with genetic alterations of ALK. This must be considered when reviewing and funding treatments for NSCLC patients with this

The overall survival benefit in Chinese ALK+ NSCLC patients received targeted therapies

“…Several clinical trials and meta-analyses have found an increase in PFS among patients treated with crizotinib compared to those treated with conventional chemotherapy (3,4,24), but no significant increase in OS has been found (6,23,25). The lack of benefit in terms of OS is probably due to the cross-over between the control and experimental arms, and the subsequent therapies.…”

Moderne Tumortherapien und ihre pulmonalen Nebenwirkungen

“…Eine Übersicht über gängige Wirkstoffe aus der Gruppe dieser antineoplastischen Medikamente mit pneumotoxischem Potenzial gibt Tab. 1 [ 4 , 5 , 6 ]. Im Jahr 2003 wurde erstmals über Fälle von schwerem akuten Lungenversagen (ALI) nach Gabe von Gefitinib

Gefitinib

bei NSCLC berichtet [ 7 ].…”

Immunotherapy in Non-Small Cell Lung Cancer With Actionable Mutations Other Than EGFR

“…ALK fusions are seen in 3-5% of NSCLC patients and are more common among the following groups: no prior smoking history, adenocarcinoma histology, younger age, female gender, and tumors with wild type EGFR and KRAS (16,(19)(20)(21). Several ALK inhibitors have been approved by the FDA for metastatic NSCLC, including crizotinib, brigatinib, alectinib, lorlatinib and ceritinib (22)(23)(24)(25)(26)(27)(28)(29). The data on the efficacy of ICIs in the ALK fusion positive NSCLC has been scarce.…”