Alk Mutations in Patients With Non-small Cell Lung Cancer a Systematic Review and Meta-analysis

Groundwork: Crizotinib and alectinib are the 2 most commonly used anaplastic lymphoma kinase (ALK) inhibitors for ALK-positive non-pocket-sized cell lung cancer (NSCLC). We compared their antitumor efficacies and adverse effects based on a pooled assay of the ALEX, ALESIA, and J-ALEX clinical trials. Methods: Seven databases were searched for eligible articles. The chief endpoints included overall survival (Os), progression-free survival (PFS), cardinal nervous organization (CNS)-PFS, drug responses, and adverse effects (AEs). Results: Seven articles on iii randomized controlled clinical trials (ALEX, ALESIA, and J-ALEX) that included 697 patients were included. Compared with crizotinib, alectinib exhibited superior efficacy in PFS (HR [take chances ratio]: 0.35 [0.25–0.49], p < 0.00001), Bone (Hour: 0.66 [0.47–0.92], p = 0.02), CNS-PFS (HR: 0.17 [0.11–0.24], p < 0.00001), elapsing of response (Hr: 0.31 [0.23–0.42], p < 0.00001), objective response rate (risk ratio [RR]: 0.87 [0.fourscore–0.94], p = 0.0003), partial response (RR: 0.88 [0.81–0.96], p = 0.004), and grade iii–5 AEs (RR: 1.43 [one.09–1.87], p = 0.009). Additionally, compared with crizotinib, alectinib exhibited a survival advantage that increased with its prolongation of survival time. The disease command rate, complete response, and full AEs were comparable between the two groups. The crizotinib grouping reported higher rates of constipation, nausea, diarrhea, vomiting, peripheral edema, dysgeusia, visual damage, and levels of alanine aminotransferase and aspartate aminotransferase equally well equally greater decreases in appetite and neutrophil count. Conclusions: In both antitumor efficacy and safety, alectinib appears to be superior to crizotinib for the treatment of ALK-positive NSCLC.

© 2022 S. Karger AG, Basel

Introduction

Over the last decade, lung cancer has become the leading cause of cancer-related death, and 80% of all lung cancers are non-small cell lung cancer (NSCLC) [1]. Approximately iii%–7% of all patients with NSCLC have anaplastic lymphoma kinase (ALK)-positive disease [2]. Crizotinib, the first clinically established ALK inhibitor, exhibits satisfactory antitumor efficacy and safety compared with chemotherapy for treatment of ALK-positive NSCLC [3, 4]. However, frequent crizotinib resistance and poor central nervous system (CNS) efficacy are very troubling for clinicians [5].

Alectinib, the most usually used second-generation ALK inhibitor, is constructive confronting several ALK mutations and exhibits loftier selectivity and CNS activity [6, vii]. In the AF-001JP clinical trial, Seto et al. [8] demonstrated that alectinib is highly constructive for the treatment of ALK-positive NSCLC. However, whether alectinib can replace crizotinib as the first-line treatment for patients with ALK-positive NSCLC remains controversial [9, 10]. Peters et al. [11] reported that alectinib achieves better progression-free survival (PFS) and has fewer agin effects (AEs) than crizotinib in treatment of ALK-positive NSCLC. Hida et al. [12] and Nishio et al. [xiii] suggested that alectinib could preclude new brain metastasis and avoid the progression of encephalon metastases. In the ALESIA clinical trial, Zhou et al. [14] confirmed that alectinib treatment results in improved clinical benefits, east.g., PFS and CNS-PFS, for ALK-positive NSCLC. However, a statistically significant advantage of overall survival (OS) was still not confirmed in the ALEX, ALESIA, or J-ALEX trials [11, 12, 14]. Bedas et al. [15] reported that crizotinib and alectinib treatments were associated with similar PFS and Bone rates in elderly patients with advanced ALK-positive NSCLC. To further clarify this fence, we compared the efficacy and safety of crizotinib with those of alectinib for treatment of ALK-positive NSCLC by performing a meta-assay of the relevant literature.

Materials and Methods

Nosotros conducted this study according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines (online suppl. Table S1; for all online suppl. material, run across www.karger.com/doi/x.1159/000521452) (Registration data: PROSPERO CRD42020185135).

Search Strategy

PubMed, EMBASE, Scopus, Ovid MEDLINE, Web of Science, the Cochrane Library, ScienceDirect, and Google Scholar were rigorously searched for eligible randomized, controlled trials (RCTs) from inception to March 5, 2021. As key words, we used "lung cancer," "crizotinib," and "alectinib." We besides searched the reference lists of the included RCTs to place additional eligible studies. Details tin can be found in online supplementary Table S2.

Selection Criteria

Studies that met the post-obit criteria were enrolled in accord with PICOS (Participants, Intervention, Control, Effect, Written report pattern):

1. Population (P): patients with ALK-positive NSCLC;

2. Intervention (I) and comparison (C): crizotinib versus alectinib;

3. Outcomes (O): antitumor efficacy and AEs (see the Data Extraction section);

4. Study design (South): RCTs published in English language.

The post-obit articles were excluded: articles without initial data, meta-analyses, conference articles, instance reports, and articles from the same experimental centre on the aforementioned topic. Dissimilar articles that focused on the aforementioned trial were included if they contained different outcomes; however, when analyzing the same consequence, only the nearly recent information were used.

Data Extraction

The post-obit data were extracted by 2 contained investigators: the written report characteristics (e.g., publication date, first author, and pattern), participant characteristics (e.g., number, sex, and age), cancer characteristics (due east.g., histopathology, stage, and ALK condition), antitumor efficacy (e.m., Bone, PFS, CNS-PFS, and drug responses), and number of AEs (total AEs, course 3–5 AEs, treatment discontinuation, dose reduction, and dose interruption). All information assessed by the contained review committee (IRC) and investigators were extracted. All disagreements between the 2 investigators were resolved through reexamination and discussion.

Outcome Assessments

OS, PFS, and CNS-PFS were the primary endpoints analyzed. In addition to analyzing the time-to-effect data, we compared the rates of survival (OS rate [OSR], PFS rate [PFSR], and CNS-PFS rate [CNS-PFSR]) at 6, 12, 18, 24, and xxx months (OSR 6–30 months, PFSR 6–thirty months, and CNS-PFSR 6–thirty months) between the 2 groups. Additionally, we analyzed PFS co-ordinate to the following subgroups: age, sex, smoking condition, CNS metastases at baseline, race category, treatment line, previous encephalon radiation, disease stage, and the ALK testing method.

Quality Assessment

The quality of RCTs was assessed using the 5-point Jadad scale and the Cochrane Take a chance Cess Tool. The Jadad scale is primarily used to evaluate quality based on randomization, blinding, and patient inclusion. A study is regarded as high quality if it receives a score of ≥3 points [16]. The Cochrane Gamble Assessment Tool primarily focuses on the bias of option, functioning, detection, attrition, and reporting, and the adventure is assessed as low, unclear, or loftier hazard [17]. Then, the results are presented every bit a risk of bias graph.

The quality of the results was assessed using the Grading of Recommendations, Cess, Development, and Evaluation (Course) method [eighteen]. The GRADE approach primarily focuses on bias, discordance, indirectness, inaccuracy, and publication bias. The results include 4 levels: very low, low, medium, and high.

Statistical Analysis

We used Review Manager 5.3 software (Nordic Cochrane Centre, Oxford, Uk) to evaluate the pooled data. The take chances ratio (60 minutes) was used to clarify the survival data (Bone, PFS, and CNS-PFS). All of the HR data were directly extracted from the included studies. When the HR was <i, the results supported the alectinib group. The risk ratio (RR) was used to analyze the dichotomous variables (drug responses, OSR, PFSR, CNS-PFSR, and AEs). When the RR was >1, and so the results supported the alectinib group, equally in the analysis of AEs, or the results supported the crizotinib group, equally in the analysis of OSR, PFSR, CNS-PFSR, and AEs. The antitumor efficacy information assessed past the IRC and investigators were analyzed separately. We used the I ^two statistic and χⁱⁱ test to evaluate the heterogeneity. If I ² < 50% or p > 0.i, indicating no significant heterogeneity, so we used a fixed-effects model; otherwise, we used a random-effects model. Statistical significance was indicated by p < 0.05. Publication bias was assessed by performing a visual check of the funnel plots.

Results

Search Results

Seven manufactures on three RCTs (ALEX, ALESIA, and J-ALEX) that included 697 patients (317 patients in the crizotinib arm and 380 patients in the alectinib arm) were included in the concluding analysis [11-fourteen, 19-21] (Fig. ane). The ALESIA and J-ALEX trials [12, fourteen] were conducted in Asia, but the ALEX trial included participants from 32 countries all over the earth [eleven]. All three of these studies were of high quality co-ordinate to the Cochrane Take a chance of Bias Tool (online suppl. Fig. S1) and the Jadad scale (online suppl. Tabular array S3). According to the Class method, all of the results were of medium-high quality (online suppl. Table S4). Essential information from the ALEX, ALESIA, and J-ALEX clinical trials is summarized in Tabular array 1.

Table i.

Characteristics of the iii randomized controlled trials (ALEX, ALESIA, and J-ALEX)

Fig. 1.

Flowchart of study selection.

Antitumor Efficacy

3 studies compared the OS of the alectinib group versus the crizotinib group (heterogeneity: I ² = 55%, p = 0.02). The Os of the alectinib group was better than that of the crizotinib group (HR: 0.66, 95% confidence interval [CI]: [0.47–0.92], p = 0.02; Fig. ii). The OSR at all time points tended to favor the alectinib group but was not significantly different between the groups (OSR-6 months, RR: 0.97 [0.91–1.04], p = 0.36; OSR-12 months, RR: 0.89 [0.79–1.02], p = 0.09; OSR-18 months, RR: 0.83 [0.68–1.00], p = 0.05; OSR-24 months, RR: 0.74 [0.50–1.09], p = 0.13; and OSR-30 months, RR: 0.76 [0.52–1.11], p = 0.16; online suppl. Fig. S2). With prolonged survival, alectinib exhibited an increased advantage in Os compared with crizotinib (Fig. 3a; online suppl. Fig. S3a).

Fig. 2.

Forest plots of OS, PFS, CNS-PFS, and DOR associated with crizotinib versus alectinib.

Fig. 3.

Line charts of OSR (half-dozen–30 months; a), PFSR (6–30 months; b), and CNS-PFSR (6–xxx months; c) associated with crizotinib versus alectinib according to survival fourth dimension.

Three studies compared the PFS of the alectinib group versus the crizotinib group (heterogeneity: I ⁱⁱ = 56%, p = 0.ten). The PFS of the alectinib group was better than that of the crizotinib group (HR: 0.35 [0.25–0.49], p < 0.00001; Fig. 2). The PFSR at all time points significantly favored the alectinib group (PFSR-6 months, RR: 0.87 [0.81–0.95], p = 0.0009; PFSR-12 months, RR: 0.63 [0.55–0.72], p < 0.00001; PFSR-18 months, RR: 0.51 [0.43–0.62], p < 0.00001; PFSR-24 months, RR: 0.38 [0.27–0.53], p < 0.00001; and PFSR-30 months, RR: 0.39 [0.27–0.56], p < 0.00001; online suppl. Fig. S4). With prolonged survival, alectinib showed an increased reward in PFS compared with crizotinib (Fig. 3b; online suppl. Fig. S3b). In the subgroup analysis, significant changes in PFS were not observed according to age, sexual practice, race category, or treatment line. Smoking status (active smoker), Eastern Cooperative Oncology Group-performance condition (ECOG-PS) 2, disease stage (postoperative recurrence), and the ALK testing method (opposite transcription-polymerase chain reaction [RT-PCR]) might exist unfavorable factors for alectinib treatment. However, baseline CNS metastases and previous brain radiation might exist favorable factors for alectinib handling (Fig. four).

Fig. iv.

Forest plots of PFS in patient subgroups.

Three studies compared the CNS-PFS of the alectinib grouping versus the crizotinib group (heterogeneity: I ² = 0%, p = 0.71). The CNS-PFS of the alectinib group was better than that of the crizotinib group (Hr: 0.17 [0.11–0.24], p < 0.00001; Fig. two). The CNS-PFSR at all fourth dimension points significantly favored the alectinib group (CNS-PFSR-6 months, RR: 0.88 [0.80–0.96], p = 0.005; CNS-PFSR-12 months, RR: 0.lxx [0.64–0.76], p < 0.00001; CNS-PFSR-18 months, RR: 0.66 [0.60–0.73], p < 0.00001; CNS-PFSR-24 months, RR: 0.58 [0.51–0.66], p < 0.00001; and CNS-PFSR-30 months, RR: 0.58 [0.47–0.72], p < 0.00001; online suppl. Fig. S5). With prolonged survival, alectinib exhibited an increased advantage in CNS-PFS compared with crizotinib (Fig. 3c; online suppl. Fig. S3c).

Three studies compared the duration of response (DOR) of the alectinib group versus the crizotinib group (heterogeneity: I ^two = 0%, p = 0.41). The DOR of the alectinib group was better than that of the crizotinib group (HR: 0.31 [0.23–0.42], p < 0.00001; Fig. 2). The objective response rate (ORR) (74.45% vs. 86.58%, RR: 0.87 [0.80–0.94], p = 0.0003) and the partial response [PR] (71.92% vs. 82.11%, RR: 0.88 [0.81–0.96], p = 0.004) were meliorate in the alectinib grouping. The disease control rate [DCR] (90.54% vs. 94.21%, RR: 0.95 [0.88–1.04], p = 0.27) and the consummate response [CR] (2.52% vs. 4.47%, RR: 0.57 [0.26–ane.32], p = 0.20) were similar between the groups. Due to the high ORR and like DCR in the alectinib grouping, less stable illness [SD] (16.09% vs. 7.63%, RR: ii.01 [13.ane–3.10], p = 0.001) was found in the alectinib grouping (Fig. v).

Fig. v.

Forest plots of drug responses (ORR, DCR, CR, PR, and SD) associated with crizotinib versus alectinib.

Subgroup analysis was conducted according to whether patients had baseline CNS metastases. In patients with CNS lesions at baseline, alectinib was superior to crizotinib in PFS (60 minutes: 0.23 [0.11–0.49], p = 0.0001), systemic progression without previous CNS disease progression (Hr: 0.35 [0.xv–0.83], p = 0.02), and CNS progression without previous systemic disease progression (Hour: 0.xviii [0.09–0.36], p < 0.00001). In patients without CNS lesions at baseline, the alectinib group also had better PFS (60 minutes: 0.43 [0.thirty–0.lx], p < 0.00001) and CNS progression without previous systemic affliction progression (HR: 0.fourteen [0.06–0.33], p < 0.00001) than the crizotinib grouping. Similar mortality without previous CNS or systemic disease progression was establish between patients with or without CNS lesions at baseline in the two groups (online suppl. Table S5).

All 3 studies reported data on survival and drug responses based on both IRC assessment and investigator assessment. Co-ordinate to the assessment of the IRC, the alectinib grouping had better Bone (60 minutes: 0.66 [0.47–0.92], p = 0.02), PFS (HR: 0.42 [0.34–0.52], p < 0.00001), CNS-PFS (Hr: 0.18 [0.eleven–0.27], p < 0.00001), and DOR (HR: 0.32 [0.17–0.threescore], p = 0.0004) than the crizotinib group. According to the cess of the investigators, the alectinib grouping likewise had improve Os (HR: 0.66 [0.47–0.92], p = 0.02), PFS (HR: 0.35 [0.25–0.49], p < 0.00001), CNS-PFS (60 minutes: 0.xiv [0.06–0.31], p < 0.00001), and DOR (HR: 0.31 [0.22–0.43], p < 0.00001) than the crizotinib group (online suppl. Table S6). Online supplementary Table S6 shows the results of responses and CNS responses assessed past the IRC and investigators.

Toxicity

In summary, crizotinib treatment was associated with more course three–five AEs (53.63% vs. 37.37%, RR: 1.43 [1.09–ane.87], p = 0.009). The full AEs (98.74% vs. 98.16%, RR: 1.01 [0.99–1.03], p = 0.forty), serious AEs (29.02% vs. 24.47%, RR: 1.12 [0.88–1.44], p = 0.34), fatal AEs (iii.xv% vs. two.11%, RR: ane.51 [0.62–3.69], p = 0.37), AEs leading to treatment discontinuation (fifteen.77% vs. 10.79%, RR: 1.37 [0.93–2.02], p = 0.eleven), AEs leading to dose reduction (21.13% vs. xix.86%, RR: 1.11 [0.77–i.sixty], p = 0.57), AEs leading to dose break (39.43% vs. 26.58%, RR: 1.38 [0.90–2.12], p = 0.fifteen), and death (0% vs. 0.53%, RR: 0.twenty [0.01–4.16], p = 0.30) were comparable between the 2 groups (Tabular array 2).

Table two.

Summary of agin events

Subgroup analysis of the total AEs revealed that the crizotinib group reported higher rates of constipation, nausea, diarrhea, airsickness, peripheral edema, dysgeusia, visual impairment, and levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) too as greater decreases in appetite and neutrophil count. However, increased blood bilirubin, bronchitis, and anemia were reported in the alectinib group. Full AEs with an incidence greater than ten% in the combined crizotinib and alectinib groups are summarized in Table 3 and online supplementary Tabular array S7 and S8.

Table 3.

Full agin events with an incidence of greater than 10% according to combination of the 2 groups

In the subgroup analysis of grade three–v AEs, the crizotinib grouping exhibited a greater ALT level increase, AST level increase, neutrophil count subtract, electrocardiogram QT prolongation, nausea increment, and vomiting increase. However, anemia was reported in the alectinib group. Grade 3–five AEs with an incidence greater than 1% in the combined crizotinib and alectinib groups are summarized in Table 4 and online supplementary Table S9 and S10.

Table 4.

Course three–5 adverse events with an incidence of greater than ten% according to combination of the two groups

Publication Bias

The funnel plots for publication bias co-ordinate to the summary of survival (online suppl. Fig. S6a) and safety (online suppl. Fig. S6b) demonstrated marked evidence of symmetry, indicating an acceptable publication bias. The combined effect size (summary of survival, Z value of 14.56, p < 0.00001; summary of condom, Z value of four.99, p < 0.00001) indicated that the fail-safe N value was relevant.

Discussion

ALK-positive lung cancer accounts for 3%–7% of all lung cancer cases and in the past was one of the genetic markers that indicated poor prognosis [2, 22]. Recently, survival of patients with ALK-positive NSCLC has been greatly improved post-obit the discovery and use of ALK inhibitors [23, 24]. Every bit the representative first- and 2d-generation ALK inhibitors, crizotinib and alectinib accept been widely used in clinical do, and their efficacy and safety have been assessed [nineteen, xx]. Yet, whether alectinib exhibits superior antitumor efficacy to crizotinib for the handling of ALK-positive NSCLC, especially equally a outset-line treatment, remains controversial [9, 10]. This is the starting time meta-analysis that focuses on the comparison of crizotinib with alectinib in ALK-positive NSCLC patients based on 3 high-quality RCTs (the ALEX, ALESIA, and J-ALEX clinical trials). In summary, alectinib therapy had improve efficacy than crizotinib therapy with regard to OS, PFS, CNS-PFS, DOR, ORR, PR, and form 3–5 AEs. Additionally, the survival advantages of alectinib over crizotinib increased with the prolongation of survival time. Similar DCR, CR, and total AEs were establish in the 2 groups.

Better survival, specially command of CNS metastases, is the primary benefit of alectinib treatment. The advantages of alectinib are significant in both first-line and 2d-line treatment of ALK-positive NSCLC. Camidge et al. [20] analyzed the well-nigh contempo data of the ALEX written report and plant that alectinib therapy could greatly prolong the PFS of patients with ALK-positive NSCLC compared with crizotinib therapy (34.8 months vs. 10.9 months, HR: 0.43, 95% CI: 0.32–0.58). Similar results were confirmed in the ALESIA written report [14]. Nishio et al. [13] analyzed the CNS efficacy in the J-ALEX trial and plant that alectinib could delay encephalon metastasis and averted the progression of brain metastases. A study by Gadgeel et al. [19] based on the ALEX trial reported superior CNS activeness of alectinib therapy for ALK-positive NSCLC regardless of CNS affliction or radiotherapy at baseline. 5 reasons may explain the benefits observed with alectinib therapy. Starting time, equally a highly selective ALK inhibitor, alectinib targets a significantly dissimilar ALK tyrosine kinase domain than does crizotinib, which can overcome the secondary mutation of the kinase domain acquired past crizotinib [25]. Second, alectinib can inhibit more ALK mutations (such as EML4-ALK, G1269A, C1156Y, F1174L, 1151Tin, and L1152R), which were identified in lung cancer tissues of crizotinib-resistant patients [vi]. Third, alectinib has a stronger affinity for the ALK tyrosine kinase domain, which can increase the depth of response and prolong the DOR (HR: 0.31 [0.23–0.42], p < 0.00001), resulting in a longer PFS [26]. Fourth, alectinib (which is not a substrate of P-glycoprotein) can penetrate into the CNS more effectively than crizotinib and delay brain metastasis [27]. 5th, a college frequency of AEs during crizotinib therapy resulted in shorter treatment durations [eleven, 12, 14]. Subgroup analysis of PFS suggested that existence an active smoker, having an ECOG-PS of 2, having postoperative recurrence, and RT-PCR equally the ALK testing method might be unfavorable factors for alectinib treatment. Withal, baseline CNS metastases and previous encephalon radiation might exist favorable factors for alectinib treatment. Additionally, the survival advantages of alectinib over crizotinib increased with the prolongation of survival. Ito et al. [28] and Watanabe et al. [29] reported that sequential therapy with crizotinib and alectinib later on crizotinib failure could provide a meliorate survival do good than therapy with alectinib or crizotinib solitary in patients with ALK-positive NSCLC. Alectinib was too canonical by the FDA for the handling of metastatic, ALK+ NSCLC following crizotinib therapy [24]. In summary, we believe that alectinib is a meliorate choice for ALK-positive NSCLC get-go-line treatment or 2nd-line handling, especially for patients with baseline CNS metastases and/or previous brain radiation.

Relatively good safety is another advantage of handling with alectinib, although alectinib does have a longer treatment duration. Thirteen AEs with an incidence of >twenty% were reported in the crizotinib group (nausea, diarrhea, constipation, vomiting, increased ALT level, dysgeusia, visual harm, increased AST level, decreased appetite, peripheral edema, decreased neutrophil count, pyrexia, and nasopharyngitis) compared with 8 AEs in the alectinib group (constipation, upper respiratory tract infection, increased blood bilirubin, increased bilirubin conjugated, increased blood alkali metal phosphatase, nasopharyngitis, increased ALT level, and increased creatine phosphokinase). Additionally, 15 class three–v AEs were reported with an incidence greater than 2% in the crizotinib group (increased ALT level, decreased neutrophil count, increased AST level, abnormal hepatic part, pulmonary embolism, prolonged electrocardiogram QT, neutropenia, interstitial lung disease, decreased white blood prison cell count, nausea, hyponatremia, increased creatine phosphokinase, pneumonitis, decreased appetite, and vomiting) compared with 9 in the alectinib group (anemia, increased AST level, increased creatine phosphokinase, maculopapular rash, pneumonia, interstitial lung disease, increased ALT level, urinary tract infection, and astute kidney injury). The frequency of AEs was similar to that of a previous study by Seto et al. [8] of the phase ane–2 studies. Hida et al. [12] reported that AEs acquired more discontinuations and dose interruptions during crizotinib treatment, which might also decrease the efficacy of the drug. Hou et al. [thirty] evaluated the safety of all approved ALK inhibitors and suggested that alectinib was the safest ALK inhibitor. In the subgroup assay, more gastrointestinal disorders, nervous system disorders, eye disorders, and metabolism disorders were establish in the crizotinib group. Even so, the alectinib treatment seemed to crusade more AEs related to the urinary system, musculoskeletal and connective tissue, and the respiratory system. In summary, although alectinib is safer than crizotinib for patients with ALK-positive NSCLC, its loftier frequency of form iii–v AEs should be considered during treatment.

The current meta-assay had several limitations. Outset, we included only manufactures written in English, which introduces a language bias. Second, only 3 RCTs were included, which decreases the clinical value of the combined data. 3rd, like most other meta-analyses, all information in our analysis were extracted from previously published articles, which increases the heterogeneity of data in the merged assay. Quaternary, 532/697 patients were from Asia, which decreases the clinical value in other regions. Fifth, significant heterogeneity was plant in the assay of OSR, CNS-PFSR-half dozen one thousand, and DCR, which decreased the quality of these results. 6th, private patient data meta-analysis and treatment sequence of crizotinib and alectinib were not conducted due to a lack of information, which might decrease the clinical value of the results. Seventh, the median follow-up time was dissimilar among trials, which might increment data heterogeneity between the included studies.

Conclusion

Alectinib exhibited better OS, PFS, CNS-PFS, and safety than crizotinib; thus, alectinib appears to be superior to crizotinib for the handling of ALK-positive NSCLC. The survival advantages of alectinib increased with the prolongation of survival time. Baseline CNS metastases and previous encephalon radiation might be favorable factors for alectinib treatment. Although alectinib is safer than crizotinib, its high frequency of grade three–five AEs (37.37%) should be considered during treatment. Additionally, the existing shortcomings of this meta-analysis crave further extensive and loftier-quality trials to resolve and confirm our conclusions.

Acknowledgments

The authors thank Professor Jichun Liu, MD (Department of Cardio-Thoracic Surgery, The 2d affiliated hospital of Nanchang University) for his advice and Professor Xiaoshu Cheng, Medico, PhD (Section of Cardiology, The 2d affiliated hospital of Nanchang Academy) for his data drove.

Statement of Ethics

Due to the nature of this study, no ethical approval was required.

Conflict of Interest Argument

The authors certify that there are no conflicts of interest regarding this manuscript.

Funding Sources

This study was supported by the National Natural Scientific discipline Foundation of Red china (NSFC), Grant No. (81560345), and the Natural Science Foundation of Jiangxi Province (Grant No. 20181BBG78023). The funding had no role in the design and comport of the study; drove, management, analysis, and estimation of the information; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Author Contributions

Qinghua Zeng had total access to all of the information in the manuscript and takes responsibleness for the integrity of the information and the accuracy of the data analysis. Concept and design: all authors. Acquisition, analysis, or estimation of data: all authors. Drafting of the manuscript: Qinghua Zeng and Lin Zeng. Disquisitional revision of the manuscript for important intellectual content: Qinghua Zeng, Xiquan Zhang, Shan He, Zhiyong Zhou, Luping Xia, and Wenxiong Zhang. Statistical assay: Qinghua Zeng, Lin Zeng, and Wenxiong Zhang. Supervision: Qinghua Zeng and Wenxiong Zhang.

Data Availability Statement

The data sets used and/or analyzed during the current study are bachelor from the respective author on reasonable request.

---

Author Contacts

Lin Zeng, figozl@163.com

---

Article / Publication Details

Showtime-Page Preview

Received: September 22, 2021
Accustomed: December 10, 2021
Published online: December 14, 2021

Number of Print Pages: 14
Number of Figures: 5
Number of Tables: 4

ISSN: 0009-3157 (Print)
eISSN: 1421-9794 (Online)

For additional data: https://world wide web.karger.com/CHE

---

Copyright / Drug Dosage / Disclaimer

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or past any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval organization, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage prepare along in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the abiding flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly of import when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the private authors and contributors and not of the publishers and the editor(south). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibleness for whatever injury to persons or property resulting from whatever ideas, methods, instructions or products referred to in the content or advertisements.

phillipsristraid1999.blogspot.com

Source: https://www.karger.com/Article/FullText/521452

Share this post