scholarly journals Crizotinib versus alectinib for treatment of ALK-positive non-small cell lung cancer: a pooled analysis of the ALEX, ALESIA and J-ALEX clinical trials

2020 ◽  
Author(s):  
Qinghua Zeng ◽  
Xiquan Zhang ◽  
Shan He ◽  
Zhiyong Zhou ◽  
Luping Xia ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Clinical Trials ◽  
Adverse Effects ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Pooled Analysis ◽  
Small Cell ◽  
Small Cell Lung ◽  
Anaplastic Lymphoma ◽  
Alk Positive

Abstract Background: Crizotinib and alectinib were the two most commonly used anaplastic lymphoma kinase (ALK) inhibitors for ALK-positive non-small cell lung cancer (NSCLC). We compared their antitumor efficacies and adverse effects based on a pooled analysis of the ALEX, ALESIA and J-ALEX clinical trials.Methods: Seven databases were searched for eligible articles. The primary endpoints included overall survival (OS), progression-free survival (PFS), central nervous system (CNS)-PFS, drug responses and adverse effects (AEs).Results: Three randomized controlled clinical trials (ALEX, ALESIA and J-ALEX) with a total of 7 articles and 697 patients were included. Compared with crizotinib, alectinib exhibited superior efficacy in PFS (HR [hazard ratio]: 0.35, [0.25-0.49], p < 0.00001), OS (HR: 0.66, [0.47-0.92], p = 0.02), CNS-PFS (HR: 0.17, [0.11-0.24], p < 0.00001), duration of response (HR: 0.31, [0.23-0.42], p < 0.00001), objective response rate (ORR) (Risk ratio [RR]: 0.87, [0.80-0.94], p = 0.0003), partial response (PR) (RR: 0.88, [0.81-0.96], p = 0.004), and grade 3-5 AEs (RR: 1.43, [1.09-1.87], p = 0.009). Additionally, the survival advantages of alectinib compared with crizotinib increased with alectinib’s prolongation of survival time. The disease control rate, complete response and total AEs were comparable between the two groups. A greater increase in constipation, nausea, diarrhea, alanine aminotransferase, vomiting, aspartate aminotransferase, peripheral edema, dysgeusia, and visual impairment as well as a greater decrease in appetite and neutrophil count were associated with the crizotinib groupConclusions: In both antitumor efficacy and safety, alectinib appears to be superior to crizotinib for the treatment of ALK-positive NSCLC.

scholarly journals Crizotinib versus Alectinib for the Treatment of ALK-Positive Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis

Chemotherapy ◽  
2021 ◽  
Author(s):  
Qinghua Zeng ◽  
Xiquan Zhang ◽  
Shan He ◽  
Zhiyong Zhou ◽  
Luping Xia ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Clinical Trials ◽  
Adverse Effects ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Objective Response ◽  
Small Cell ◽  
Small Cell Lung ◽  
Anaplastic Lymphoma ◽  
Alk Positive

Background: Crizotinib and alectinib are the two most commonly used anaplastic lymphoma kinase (ALK) inhibitors for ALK-positive non-small cell lung cancer (NSCLC). We compared their antitumor efficacies and adverse effects based on a pooled analysis of the ALEX, ALESIA and J-ALEX clinical trials. Methods: Seven databases were searched for eligible articles. The primary endpoints included overall survival (OS), progression-free survival (PFS), central nervous system (CNS)-PFS, drug responses and adverse effects (AEs). Results: Seven articles on three 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 [hazard ratio]: 0.35, [0.25-0.49], p < 0.00001), OS (HR: 0.66, [0.47-0.92], p = 0.02), CNS-PFS (HR: 0.17, [0.11-0.24], p < 0.00001), duration of response (HR: 0.31, [0.23-0.42], p < 0.00001), objective response rate (ORR) (risk ratio [RR]: 0.87, [0.80-0.94], p = 0.0003), partial response (PR) (RR: 0.88, [0.81-0.96], p = 0.004), and grade 3-5 AEs (RR: 1.43, [1.09-1.87], p = 0.009). Additionally, compared with crizotinib, alectinib exhibited a survival advantage that increased with its prolongation of survival time. The disease control rate, complete response and total AEs were comparable between the two groups. The crizotinib group reported higher rates of constipation, nausea, diarrhea, vomiting, peripheral edema, dysgeusia, visual impairment and levels of alanine aminotransferase and aspartate aminotransferase as well as 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.

Complete response after ceritinib treatment in non-small cell lung cancer in an elderly patient

2020 ◽  
Vol 26 (8) ◽  
pp. 2031-2033
Author(s):  
Nilay Sengul Samanci ◽  
Emir Celik ◽  
Burak Akovalı ◽  
Sait Sager ◽  
Fuat Hulusi Demirelli
Keyword(s):  
Lung Cancer ◽  
Elderly Patient ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Complete Response ◽  
Small Cell ◽  
Small Cell Lung ◽  
Anaplastic Lymphoma ◽  
Stage 4 ◽  
Alk Positive

Introduction Ceritinib is a selective second-generation ALK inhibitor that is highly sensitive to echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) molecule. Case report In this paper, we report a 68-year-old female that was diagnosed with stage 4 ALK-positive non-small cell lung cancer (NSCLC). Management and outcome: She was treated with crizotinib first-line, cisplatin and gemcitabine as second-line. And for third-line, ceritinib was started. She had complete response over 3.5 years under ceritinib treatment. And she is still receiving ceritinib with no adverse event. Discussion Cases achieving complete response with ceritinib treatment are rare. In this paper, we aimed to emphasize the complete response in stage 4 NSCLC in an elderly patient.

scholarly journals Chart Review Versus an Automated Bioinformatic Approach to Assess Real-World Crizotinib Effectiveness in Anaplastic Lymphoma Kinase–Positive Non–Small-Cell Lung Cancer

2017 ◽  
pp. 1-6
Author(s):  
Nam Bui ◽  
Solomon Henry ◽  
Douglas Wood ◽  
Heather A. Wakelee ◽  
Joel W. Neal
Keyword(s):  
Lung Cancer ◽  
Clinical Trials ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Anaplastic Lymphoma Kinase ◽  
Chart Review ◽  
Computational Algorithm ◽  
Small Cell ◽  
Small Cell Lung ◽  
Anaplastic Lymphoma

Purpose The efficacy of targeted therapies such as crizotinib in anaplastic lymphoma kinase–positive non–small-cell lung cancer has been well established by multiple clinical trials. However, clinical trials involve highly selected participants, and manual data curation is resource intensive. With the increasing use of electronic medical records, there is potential for the development of electronic algorithms that could quickly generate outcomes data, but the validation of such algorithms requires comparison with historical methods, such as retrospective chart review. Materials and Methods Using a cohort of patients with anaplastic lymphoma kinase–positive non–small-cell lung cancer, we performed manual chart review to retrospectively evaluate time on treatment (TOT) for crizotinib and cytotoxic chemotherapies. Thirty-three patients were identified, with a total of 70 regimens administered. We developed a computational algorithm to mine electronic charts for crizotinib therapy data and correlated that with manually curated data. Results Among the 24 patients who received crizotinib, the median TOT was 8.5 months. The computational algorithm was able to extract TOT data for 15 out of 24 patients treated with crizotinib (62.5%). Most of the patients for whom data could not be automatically extracted were treated within a clinical trial. Pearson’s correlation coefficient between the two methods was 0.39 ( P = .15); however, there were five outliers as a result of incorrect provider notation and nonstandard treatment patterns that severely skewed the correlation. Conclusion An automated method of extracting patient TOT is feasible but requires additional optimizations to handle outliers. We are currently working on improving the algorithm to better correct for outliers. Automated generation of treatment data potentially represents a viable approach to perform retrospective outcomes analysis.

Brigatinib: Novel ALK Inhibitor for Non–Small-Cell Lung Cancer

2019 ◽  
Vol 53 (6) ◽  
pp. 621-626 ◽  
Author(s):  
Sara A. Spencer ◽  
Angela C. Riley ◽  
Adia Matthew ◽  
Anthony J. Di Pasqua
Keyword(s):  
Lung Cancer ◽  
Adverse Effects ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
English Language ◽  
Small Cell ◽  
Small Cell Lung ◽  
Once Daily ◽  
Anaplastic Lymphoma ◽  
Accelerated Approval

Objective: We review here the pharmacology, pharmacokinetics, efficacy, safety, dosage and administration, potential drug-drug interactions and place in therapy of brigatinib for abnormal anaplastic lymphoma kinase (ALK) specific non–small-cell lung cancer (NSCLC). Data Sources: A literature search using PubMed was conducted using the terms brigatinib and ALK positive NSCLC from January 2013 to November 2018. Study Selection and Data Extraction: All English-language articles evaluating brigatinib were analyzed for this review. Data Synthesis: Brigatinib was granted approval for the treatment of patients with metastatic ALK+ NSCLC who have progressed on or are intolerant to crizotinib. It is administered at a dose of 90 mg orally once daily for the first 7 days then, if tolerated, increased to a dose of 180 mg orally once daily. Common adverse effects include nausea, fatigue, diarrhea, increased creatine phosphokinase levels, headache, dyspnea, and hypertension. Serious treatment-emergent adverse effects were pulmonary related. Relevance to Patient Care and Clinical Practice: This article discusses the clinical trials that led to the accelerated approval of brigatinib for its ability to overcome crizotinib-resistant mutations and for its increased central nervous system penetration properties. Conclusion: Brigatinib was granted accelerated approval for the treatment of patients with metastatic ALK+ NSCLC who have progressed on or are intolerant to crizotinib. In a subset of NSCLC patients, brigatinib increases survival for approximately 1 year; however, side effects were detected.

scholarly journals Canadian consensus: inhibition of ALK-positive tumours in advanced non-small-cell lung cancer

2016 ◽  
Vol 23 (3) ◽  
pp. 196 ◽  
Author(s):  
B. Melosky ◽  
J. Agulnik ◽  
R. Albadine ◽  
S. Banerji ◽  
D.G. Bebb ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Alk Rearrangement ◽  
Alk Inhibitors ◽  
Anaplastic Lymphoma ◽  
Alk Positive ◽  
Nonsquamous Nsclc

Anaplastic lymphoma kinase (ALK) is an oncogenic driver in non-small-cell lung cancer (NSCLC). Chromosomal rearrangements involving the ALK gene occur in up to 4% of nonsquamous NSCLC patients and lead to constitutive activation of the ALK signalling pathway. ALK-positive NSCLC is found in relatively young patients, with a median age of 50 years. Patients frequently have brain metastasis.Targeted inhibition of the ALK pathway prolongs progression-free survival in patients with ALK-positive advanced NSCLC. The results of several recent clinical trials confirm the efficacy and safety benefit of crizotinib and ceritinib in this population.Canadian oncologists support the following consensus statement: All patients with advanced nonsquamous nsclc (excluding pure neuroendocrine carcinoma) should be tested for the presence of an ALK rearrangement. If an ALK rearrangement is present, treatment with a targeted ALK inhibitor in the first-line setting is recommended. As patients become resistant to first-generation ALK inhibitors, other treatments, including second-generation ALK inhibitors can be considered.

scholarly journals Efficacy of Crizotinib, Ceritinib, and Alectinib in ALK-Positive Non-Small Cell Lung Cancer Treatment: A Meta-Analysis of Clinical Trials

Cancers ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 526 ◽  
Author(s):  
Tung Hoang ◽  
Seung-Kwon Myung ◽  
Thu Thi Pham ◽  
Boyoung Park
Keyword(s):  
Lung Cancer ◽  
Clinical Trials ◽  
Survival Rate ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Meta Analysis ◽  
Small Cell ◽  
Small Cell Lung ◽  
Alk Inhibitors ◽  
Alk Positive

This study aimed to evaluate the efficacy of anaplastic lymphoma kinase (ALK)-inhibitors in the treatment of ALK-positive non-small cell lung cancer (NSCLC) by using a meta-analysis of clinical trials. We searched PubMed, EMBASE, Cochrane Library, and Clinicaltrials.gov by using keywords related to the topic in August 2018. The pooled effect sizes were calculated based on a random-effects model. We also performed subgroup meta-analysis by types of ALK inhibitors (crizotinib, ceritinib, and alectinib). A total of 20 clinical trials with 10 single-arm trials and 10 double-arm trials were included in the final meta-analysis. The median overall survival (OS), progression-free survival (PFS), overall response rate (ORR), disease control rate (DCR), 1 year survival rate, and 2 year survival rate were 19.14 months, 8.47 months, 62%, 78%, 74%, and 62%, respectively. ALK inhibitors showed a significantly superior efficacy compared with chemotherapy (hazard ratio (HR) for OS, 0.83; HR for PFS, 0.43; rate difference (RD) for ORR, 0.23; and RD for DCR, 0.10). The current meta-analysis of clinical trials showed the significant efficacy of ALK inhibitors in the treatment of ALK-positive NSCLC. Further head-to-head trials are needed to compare their efficacy with other types of NSCLC treatment regimens. PROSPERO registration: CRD42018085987.

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