Abstract
ObjectiveTo systematically evaluate the efficacy and safety of alectinib versus crizotinib in the treatment of anaplastic lymphoma kinase (ALK) positive non-small-cell lung cancer.MethodsStudies about the efficacy of alectinib versus crizotinib in the treatment of ALK-positive non-small cell lung cancer were searched in PubMed, Scopus, Embase and the Cocharane Library from inception to February 15, 2020. Two reviewers independently screened these studies, extracted the data, assessed the risk of bias in the included studies by using the Cochrane risk assessment tool, and then used review manager 5.3 software for meta-analysis.ResultsThree studies comprising a total of 697 patients with ALK-positive non-small cell lung cancer were included, 380 in the alectinib group and 317 in the crizotinib group. The dose of alectinib (300 mg) in J-ALEX were lower than the approved dose (600 mg), however the crizotinib group in all three studies received the recommended dose (250 mg). Performance bias was high in all three studies whereas, and the attrition bias was high in two studies (Toyoaki Hida 2017 and Solange peters 2017). The results of meta-analysis showed that: the overall response rate [OR = 2.07, 95% CI (1.41, 3.06), P = 0.0002], the progression free survival [HR = 0.34, 95% CI (0.21, 0.55), P <0.0001], the partial response [OR = 1.71, 95% CI (1.19, 2.46), P = 0.003], P = 0.001], in alectinib group were higher than that of crizotinib group. Though the total number of events in complete response and the disease control rate were more in alectinib group than that of crizotinib group, the meta-analysis results shows no significant differences between two drugs in the disease control rate [OR = 2.24, 95% CI (0.56, 8.88), P = 0.25], the complete response [OR = 1.82, 95% CI (0.75, 4.45), P = 0.19]. In addition, the number of events in the stable disease [OR = 0.45, 95% CI (0.28, O.74), P = 0.001], and the adverse events [OR = 0.50, 95% CI (0.23, 0.81), P = <0.0001] in alectinib group were lower than that of crizotinib group.ConclusionAlectinib in terms of overall response rate, progression-free survival and partial response is superior to crizotinib in the treatment of ALK-positive non-small cell lung cancer and is well tolerated. Compared with crizotinib, alectinib is more effective than crizotinib and has a lower incidence of total adverse reactions. Meta-analysis results confirm the strong base for alectinib as a first-line treatment for ALK-positive NSCLC.
Highlights
Lung cancer is the second most commonly occurring cancer worldwide accounting for 11.4% of the total new cancer cases
In recently conducted phase 3 ALTA-1L trial comparing brigatinib versus crizotinib, 275 patients were randomized; brigatinib (n = 137), crizotinib (n = 138), 26% patients in brigatinib while 27% patients in crizotinib group earlier received chemotherapy for advanced disease, 29%/30% had baseline brain metastases, at the data cutoff median follow-up was brigatinib/crizotinib: 11.0/ 9.25 months; BIRC-assessed progression-free survival (PFS) (HR 0.49, 95% CI 0.33, 0.74, p = 0.0007), brigatinib PFS, investigatorassessed PFS (HR 0.45, p = 0.0001), most common treatment related adverse events (AEs) with brigatinib were elevated creatine phosphokinase (CPK) (16.2%), elevated lipase (13.2%), hypertension (9.6%); crizotinib: increased ALT (9.5%), AST (5.8%), and lipase (5.1%)
After layer-by-layer screening according to the inclusion and exclusion criteria mentioned in Table 1, a total of 834 articles were retrieved from four databases: PubMed, Scopus, Embase and the Cocharane Library
Summary
Lung cancer is the second most commonly occurring cancer worldwide accounting for 11.4% of the total new cancer cases. Lung cancer is currently the leading cause of cancer deaths, and accounting for approximately 20% of all cancer death rate. By 2017, the incidence of lung cancer in China had risen to 800,000 cases, while the mortality had reached 700,000. This shows that China’s primary bronchial lung cancer morbidity and mortality have an alarming growth rate, non-small cell lung cancer (NSCLC) is the most common form of lung cancer, accounting for approximately 85% of all lung cancer cases [3, 4]. As it is well known that, many patients with advanced NSCLC benefit from chemotherapy to a certain level. Platinumbased chemotherapy is the standard treatment for patients with advanced NSCLC [7]. Due to aforementioned reasons, we need more and better treatment strategies for advanced NSCLC
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