scholarly journals ID:1882 Phase III Randomized Study of Ensartinib vs Crizotinib in Anaplastic Lymphoma Kinase (ALK) POSITIVE NSCLC Patients: eXalt3

2020 ◽  
Vol 15 (10) ◽  
pp. e41-e42 ◽  
Author(s):  
G. Selvaggi ◽  
H.A. Wakelee ◽  
T. Mok ◽  
Y.-L. Wu ◽  
M. Reck ◽  
...  
Keyword(s):  
Anaplastic Lymphoma Kinase ◽  
Randomized Study ◽  
Phase Iii ◽  
Anaplastic Lymphoma ◽  
Alk Positive ◽  
Nsclc Patients

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 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.

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