scholarly journals Systematic Review and Network Meta-Analysis of Anaplastic Lymphoma Kinase (ALK) Inhibitors for Treatment-Naïve ALK-Positive Lung Cancer

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1966
Author(s):  
Cheng-Hao Chuang ◽  
Hsiao-Ling Chen ◽  
Hsiu-Mei Chang ◽  
Yu-Chen Tsai ◽  
Kuan-Li Wu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Brain Metastasis ◽  
Anaplastic Lymphoma Kinase ◽  
Low Dose ◽  
Meta Analysis ◽  
Phase Iii ◽  
Pairwise Comparisons ◽  
Anaplastic Lymphoma ◽  
Treatment Naïve ◽  
Alk Positive

Several anaplastic lymphoma kinase inhibitors (ALKIs) have demonstrated excellent efficacy on overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and also better adverse effect (AE) profiles compared to cytotoxic chemotherapy in advanced stage anaplastic lymphoma kinase (ALK) rearrangement-positive non-small cell lung cancer (NSCLC) in phase III randomized clinical trials (RCTs). We conducted this systematic review and network meta-analysis to provide a ranking of ALKIs for treatment-naïve ALK-positive patients in terms of PFS, ORR, and AEs. In addition, a sub-group analysis of treatment benefits in patients with baseline brain metastasis was also conducted. Contrast-based analysis was performed for multiple treatment comparisons with the restricted maximum likelihood approach. Treatment rank was estimated using the surface under the cumulative ranking curve (SUCRA), as well as the probability of being the best (Prbest) reference. All next-generation ALKIs were superior to crizotinib in PFS but lorlatinib and brigatinib had increased AEs. The probability of lorlatinib being ranked first among all treatment arms was highest (SUCRA = 93.3%, Prbest = 71.8%), although there were no significant differences in pairwise comparisons with high- (600 mg twice daily) and low- (300 mg twice daily) dose alectinib. In subgroup analysis of patients with baseline brain metastasis, low-dose alectinib had the best PFS (SUCRA = 87.3%, Prbest = 74.9%). Lorlatinib was associated with the best ranking for ORR (SUCRA = 90.3%, Prbest = 71.3%), although there were no significant differences in pairwise comparisons with the other ALKIs. In addition, low-dose alectinib had the best safety performance (SUCRA = 99.4%, Prbest = 97.9%). Lorlatinib and low-dose alectinib had the best PFS and ORR in the overall population and baseline brain metastasis subgroup, respectively. Low-dose alectinib had the lowest AE risk among the available ALKIs. Further head-to-head large-scale phase III RCTs are needed to verify our conclusions.

scholarly journals First-Line Anaplastic Lymphoma Kinase (ALK) Inhibitors for ALK-Positive Lung Cancer in Asian Populations: Systematic Review and Network Meta-Analysis

2021 ◽  
Vol 10 (19) ◽  
pp. 4376
Author(s):  
Kuan-Li Wu ◽  
Hsiao-Ling Chen ◽  
Ying-Ming Tsai ◽  
Tai-Huang Lee ◽  
Hsiu-Mei Chang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Clinical Trials ◽  
Anaplastic Lymphoma Kinase ◽  
Kinase Inhibitors ◽  
Meta Analysis ◽  
Phase Iii ◽  
First Line ◽  
Anaplastic Lymphoma ◽  
Asian Populations ◽  
Alk Positive

Various anaplastic lymphoma kinase inhibitors (ALKIs) have been approved for first-line use in treating anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC). To date, no head-to-head comparison of these newer generation ALKIs has been made, and different efficacies of ALKIs may present across ethnicity. This study aims to compare newer generation ALKIs for treatment efficacy in Asian groups using network meta-analysis. Phase II/III trials that enrolled treatment-naïve Asian ALK-rearranged NSCLC patients treated by ALKIs were included. Progression-free survival (PFS) and overall response rate (ORR) of each trial were extracted as indicators of drug efficacy. Surfaces under cumulative ranking curves (SUCRAs) were calculated as a numeric presentation of the overall ranking associated with each agent. After a systematic literature review, six phase III clinical trials were included. Our results showed that newer generation ALKIs, such as alectinib, brigatinib, ensartinib, and lorlatinib, all demonstrated superior efficacy to crizotinib. Among those, ensartinib exhibited the best overall SUCRA value and ranked first among all agents. According to our network meta-analysis, ensartinib may currently be the most effective first-line treatment for Asian patients with ALK-positive NSCLC. However, this conclusion needs further validation by a larger scale of clinical trials or posthoc analysis of Asian populations. Moreover, in our comparison, low-dose alectinib (300 mg twice daily) exhibited an efficacy profile similar to a higher dose regimen in Asian populations.

eXalt3: A phase III study of ensartinib (X-396) in anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. TPS8578-TPS8578 ◽  
Author(s):  
Leora Horn ◽  
Yi-Long Wu ◽  
Martin Reck ◽  
Chris Liang ◽  
Fenlai Tan ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Anaplastic Lymphoma Kinase ◽  
Small Cell ◽  
Phase Iii ◽  
Small Cell Lung ◽  
Prior Chemotherapy ◽  
Anaplastic Lymphoma ◽  
Phase Iii Study ◽  
Alk Positive ◽  
Nsclc Patients

TPS8578 Background: Ensartinib is a novel, potent anaplastic lymphoma kinase (ALK) small molecule tyrosine kinase inhibitor (TKI) with additional activity against MET, ABL, Axl, EPHA2, LTK, ROS1 and SLK. Ensartinib has demonstrated activity in ALK treatment naïve and previously treated patients and has a generally well tolerated safety profile. Methods: eXalt3 (NCT02767804) is a global, randomized, open-label phase III study comparing the efficacy and safety of ensartinib to crizotinib in ALK- positive TKI naïve non-small cell lung cancer (NSCLC) patients. It is being conducted in > 100 sites in North America, South America, Europe, and the Asia/Pacific region. Enrollment began in 2016. The primary efficacy endpoint is progression free survival (PFS) assessed by independent radiology review. Secondary efficacy endpoints include overall survival, response rates (overall and central nervous system [CNS]), PFS by investigator assessment, time to response, duration of response, and time to CNS progression. Approximately 270 patients with ALK+ NSCLC who have received no prior ALK TKI and up to one prior chemotherapy regimen will be randomized 1:1 to ensartinib 225 mg QD, or crizotinib 250 mg BID, with stratification based on prior chemotherapy, ECOG performance status (PS), CNS metastases and geographic region. Eligibility includes patients ≥ 18 years of age, stage IIIB or IV ALK+ NSCLC. Patients are required to have measurable disease per RECIST 1.1, adequate organ function, and an ECOG PS of ≤2. Adequate tumor tissue (archival or fresh biopsy) must be available for central testing. The study has > 80% power to detect a superior effect of ensartinib over crizotinib in PFS at a 2-sided alpha level of 0.05. Clinical trial information: NCT02767804.

scholarly journals EXalt3: A phase III study of ensartinib (X-396) in anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC)

2017 ◽  
Vol 28 ◽  
pp. ii51
Author(s):  
L. Horn ◽  
Y.-L. Wu ◽  
M. Reck ◽  
C. Liang ◽  
F. Tan ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Anaplastic Lymphoma Kinase ◽  
Small Cell ◽  
Phase Iii ◽  
Small Cell Lung ◽  
Anaplastic Lymphoma ◽  
Phase Iii Study ◽  
Alk Positive

scholarly journals Efficacy and Safety of First-Line Treatment Strategies for Anaplastic Lymphoma Kinase-Positive Non-Small Cell Lung Cancer: A Bayesian Network Meta-Analysis

2021 ◽  
Vol 11 ◽  
Author(s):  
Ling Peng ◽  
Dafeng Lu ◽  
Yang Xia ◽  
Shaodong Hong ◽  
Giovanni Selvaggi ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Anaplastic Lymphoma Kinase ◽  
Meta Analysis ◽  
Small Cell ◽  
Line Treatment ◽  
Small Cell Lung ◽  
First Line ◽  
Anaplastic Lymphoma ◽  
Alk Positive ◽  
First Line Treatment

BackgroundTargeted therapies have led to significant improvement in the management and prognosis of anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC). We performed a network meta-analysis of frontline treatment options of ALK-positive NSCLC to provide clinical guidance.MethodsPubMed, Embase, ClinicalTrials.gov, and international conference databases were searched to identify relevant trials from inception to June 30, 2021. Phase III randomized controlled trials (RCTs) comparing treatments for patients with ALK-positive advanced NSCLC in the first-line setting were included in a Bayesian network meta-analysis. Eligible studies reported at least one of the following clinical outcomes: progression-free survival (PFS), overall survival (OS), risk of the central nervous system (CNS) progression, adverse events (AEs) of grade (G) 3 or higher (G3 AEs), or serious AEs (SAEs). Hazard ratios (HRs) and CI for primary outcome of PFS and secondary outcome of OS and risk of CNS progression were obtained. A multivariate, consistency model, fixed-effects analysis was used in the network meta-analysis. Data on G3 AEs and SAEs were abstracted and meta-analyzed. Risk of bias (RoB) was assessed using the Cochrane Collaboration’s tool.ResultsNine RCTs comprising 2,484 patients were included with seven treatments: alectinib, brigatinib, ceritinib, crizotinib, ensartinib, lorlatinib, and chemotherapy. Compared with chemotherapy, ALK-tyrosine kinase inhibitors (TKIs) significantly prolong PFS and reduced risk of CNS progression except for ceritinib. Lorlatinib appears superior at reducing risk of CNS progression. None of the ALK-TKIs have a significantly prolonged OS as compared with chemotherapy. Lorlatinib increases the risk of G3 AEs as compared with alectinib (odds ratio 4.26 [95% CrI 1.22 to 15.53]), while alectinib caused the fewest G3 AEs.ConclusionsLorlatinib is associated with the highest PFS benefit and lowest risk of CNS progression benefits for patients with advanced ALK-positive NSCLC, compared with other first-line treatments, but with higher toxicity. The implementation of a newer generation of ALK-TKIs in the first-line treatment of ALK-positive NSCLC into current clinical practice is evolving rapidly.

scholarly journals Alectinib versus chemotherapy in crizotinib-pretreated anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer: results from the phase III ALUR study

2018 ◽  
Vol 29 (6) ◽  
pp. 1409-1416 ◽  
Author(s):  
S. Novello ◽  
J. Mazières ◽  
I.-J. Oh ◽  
J. de Castro ◽  
M.R. Migliorino ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Anaplastic Lymphoma Kinase ◽  
Small Cell ◽  
Phase Iii ◽  
Small Cell Lung ◽  
Anaplastic Lymphoma ◽  
Alk Positive

scholarly journals Visual Effects in Anaplastic Lymphoma Kinase (ALK)-Positive Advanced Non-Small-Cell Lung Cancer (NSCLC) Patients Treated with Crizotinib

2012 ◽  
Vol 23 ◽  
pp. xi44
Author(s):  
P.-C. Yang ◽  
R. Salgia ◽  
B. Solomon ◽  
A.T. Shaw ◽  
D.R. Camidge ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Anaplastic Lymphoma Kinase ◽  
Small Cell ◽  
Small Cell Lung ◽  
Visual Effects ◽  
Anaplastic Lymphoma ◽  
Alk Positive ◽  
Nsclc Patients
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