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.

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 Efficacy of lorlatinib in the treatment of ALK-positive non-small cell lung cancer patients with progression on crizotinib: personal experience

2021 ◽  
pp. 62-67
Author(s):  
K. K. Laktionov ◽  
E. V. Reutova ◽  
S. Yu. Kruteleva ◽  
E. Yu. Antonova
Keyword(s):  
Lung Cancer ◽  
Clinical Trials ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Kinase Inhibitor ◽  
Objective Response ◽  
Small Cell ◽  
Small Cell Lung ◽  
Alk Inhibitors ◽  
Alk Positive

Introduction. Lorlatinib is a  third generation ALK tyrosine kinase inhibitor. Back in  2018, the  drug underwent accelerated FDA approval and was recommended for the treatment of patients with ALK-positive non-small cell lung cancer after progression on crizotinib and another ALK inhibitor. For a long time, the use of the drug in Russia was possible only in clinical trials or expanded access program. However, now this drug is becoming available in our country.Purpose. To analyze the overall and intracranial response during lorlatinib therapy, as well as the tolerability of lorlatinib therapy in patients with ALK-positive non-small cell lung cancer who previously received crizotinib and one or more lines of cytostatic therapy.Materials and methods. The  study included 39  patients aged 28  to 76  years, diagnosed with non-small cell lung cancer. In 36 cases, a translocation in the ALK gene was detected, in three, a ROS1 translocation. All patients received targeted therapy with crizotinib and one or more lines of chemotherapy before starting lorlatinib therapy. All patients received 100 mg lorlatinib therapy until disease progression or intolerable toxicity.Results. During the observation period for the moment of September 2021, an objective response was achieved in 28 patients (71.7%), in 10 patients (25.6%) – stabilization of the disease, in one patient (2.6%) – progression. The median duration of the drug was just over 40 months. The drug intake was characterized by a predictable and manageable toxicity profile.Conclusions. These data indicate a high direct efficacy of lorlatinib in patients with ALK/ROS1 translocations. The data obtained do not contradict the  results obtained in  the  course of  clinical trials. The  drug lorlatinib has currently received registration in Russia for the treatment of non-small cell lung cancer in cases of the development of progression while taking secondgeneration ALK inhibitors or several lines of therapy with ALK inhibitors. 

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.

scholarly journals ALK Resistance Mutations and Efficacy of Lorlatinib in Advanced Anaplastic Lymphoma Kinase-Positive Non–Small-Cell Lung Cancer

2019 ◽  
Vol 37 (16) ◽  
pp. 1370-1379 ◽  
Author(s):  
Alice T. Shaw ◽  
Benjamin J. Solomon ◽  
Benjamin Besse ◽  
Todd M. Bauer ◽  
Chia-Chi Lin ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Second Generation ◽  
Objective Response ◽  
Progression Free Survival ◽  
Small Cell ◽  
Resistance Mutations ◽  
Small Cell Lung ◽  
Anaplastic Lymphoma

PURPOSE Lorlatinib is a potent, brain-penetrant, third-generation anaplastic lymphoma kinase (ALK)/ROS1 tyrosine kinase inhibitor (TKI) with robust clinical activity in advanced ALK-positive non–small-cell lung cancer, including in patients who have failed prior ALK TKIs. Molecular determinants of response to lorlatinib have not been established, but preclinical data suggest that ALK resistance mutations may represent a biomarker of response in previously treated patients. PATIENTS AND METHODS Baseline plasma and tumor tissue samples were collected from 198 patients with ALK-positive non–small-cell lung cancer from the registrational phase II study of lorlatinib. We analyzed plasma DNA for ALK mutations using Guardant360. Tumor tissue DNA was analyzed using an ALK mutation–focused next-generation sequencing assay. Objective response rate, duration of response, and progression-free survival were evaluated according to ALK mutation status. RESULTS Approximately one quarter of patients had ALK mutations detected by plasma or tissue genotyping. In patients with crizotinib-resistant disease, the efficacy of lorlatinib was comparable among patients with and without ALK mutations using plasma or tissue genotyping. In contrast, in patients who had failed 1 or more second-generation ALK TKIs, objective response rate was higher among patients with ALK mutations (62% v 32% [plasma]; 69% v 27% [tissue]). Progression-free survival was similar in patients with and without ALK mutations on the basis of plasma genotyping (median, 7.3 months v 5.5 months; hazard ratio, 0.81) but significantly longer in patients with ALK mutations identified by tissue genotyping (median, 11.0 months v 5.4 months; hazard ratio, 0.47). CONCLUSION In patients who have failed 1 or more second-generation ALK TKIs, lorlatinib shows greater efficacy in patients with ALK mutations compared with patients without ALK mutations. Tumor genotyping for ALK mutations after failure of a second-generation TKI may identify patients who are more likely to derive clinical benefit from lorlatinib.

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.

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