Evolution in the treatment landscape of non-small cell lung cancer with ALK gene alterations: from the first- to third-generation of ALK inhibitors

Spagnuolo, Alessia; Maione, Paolo; Gridelli, Cesare

doi:10.1080/14728214.2018.1527902

Cited by 29 publications

(18 citation statements)

References 88 publications

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“…5 ALK gene rearrangements occur in approximately 5% of NSCLC patients, indicating that ALK may represent a new and promising molecular target for NSCLC treatment. 6 To date, several ALK tyrosine kinase inhibitors (ALK-TKIs) have been developed and are widely available in clinical practice, some of which have received approval by the US Food and Drug Administration (FDA) and/or the European Medicines Agency (EMA), 7 such as crizotinib, ceritinib, alectinib, brigatinib, lorlatinib, and entrectinib.…”

Section: Introductionmentioning

confidence: 99%

<p>Pharmacokinetic-Based Drug–Drug Interactions with Anaplastic Lymphoma Kinase Inhibitors: A Review</p>

Zhao¹,

Chen²,

Chu

et al. 2020

DDDT

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Anaplastic lymphoma kinase (ALK) inhibitors are important treatment options for non-small-cell lung cancer (NSCLC), associated with ALK gene rearrangement. Patients with ALK gene rearrangement show sensitivity to and benefit clinically from treatment with ALK tyrosine kinase inhibitors (ALK-TKIs). To date, crizotinib, ceritinib, alectinib, brigatinib, lorlatinib, and entrectinib have received approval from the US Food and Drug Administration and/or the European Medicines Agency for use during the treatment of ALKgene-rearrangement forms of NSCLC. Although the oral route of administration is convenient and results in good compliance among patients, oral administration can be affected by many factors, such as food, intragastric pH, cytochrome P450 enzymes, transporters, and p-glycoprotein. These factors can result in increased risks for serious adverse events or can lead to reduced therapeutic effects of ALK-TKIs. This review characterizes and summarizes the pharmacokinetic parameters and drug-drug interactions associated with ALK-TKIs to provide specific recommendations for oncologists and clinical pharmacists when prescribing ALK-TKIs.

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Section: Introductionmentioning

confidence: 99%

<p>Pharmacokinetic-Based Drug–Drug Interactions with Anaplastic Lymphoma Kinase Inhibitors: A Review</p>

Zhao¹,

Chen²,

Chu

et al. 2020

DDDT

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“…EGFR tyrosine kinase (TK) inhibitors have been shown to be effective in patients with specific tumor cell mutations in the EGFR TK domain (3). In addition, the newly developed ALK inhibitors -ceritinib, alectinib, and brigatinib-have been approved for ALK-positive NSCLC (4). With advances in technology, more oncogenic drivers, such as ROS1, RET, BRAF, NTRK, MET, NRG1, and others, can be identified using next generation sequencing (NGS) (5).…”

mentioning

confidence: 99%

Characteristics and Clinical Outcomes of Non-small Cell Lung Cancer Patients in Korea With MET Exon 14 Skipping

Hur

Shim

et al. 2020

In Vivo

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Background/Aim: MET exon 14 skipping occurs in 3-4% of patients with lung adenocarcinomas. In this study, we performed a comprehensive analysis of clinical data from Korean non-small cell lung cancer (NSCLC) patients with MET exon 14 skipping. Patients and Methods: Overall, 1,020 patients diagnosed with NSCLC between January 2015 and July 2017 were analyzed by next-generation sequencing. Results: MET exon 14 skipping was identified in 20 NSCLC patients (1.9%). The median age was 69 years (range=39-86 years), 60.0% were male, and most (55.0%) were eversmokers. For first-line chemotherapy, the median overall survival was 9.5 months and progression-free survival was 4.0 months, respectively. Twelve patients received pemetrexed-based chemotherapy and the overall response rate was 33.3% (4/12). Among four crizotinib-treated patients, one continued therapy for 8 months with the best response being disease stability. Conclusion: Given the poor clinical outcome and response to therapy for NSCLC, and the availability of promising anti-tumor MET inhibitors, screening for the MET exon 14 skip mutation should be incorporated into clinical practice.

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“…Based on our own experience, we encourage the early review of potential side effects to minimize any impact of AEs on the quality of life of patients and to help avoid any unnecessary dose reductions or early discontinuations of this effective treatment. With the development of resistance to ALK-TKIs, later-generation ALK-TKIs have been discovered to improve safety profiles (17). However, with disease progression in patients, the switching of ALK-TKIs can be used to identify the mutations and rearrangements of ALK (11,17).…”

Section: Future Directionsmentioning

confidence: 99%

“…With the development of resistance to ALK-TKIs, later-generation ALK-TKIs have been discovered to improve safety profiles (17). However, with disease progression in patients, the switching of ALK-TKIs can be used to identify the mutations and rearrangements of ALK (11,17). In other words, it is helpful to understand the resistance mechanisms.…”

Section: Future Directionsmentioning

confidence: 99%

“…Lorlatinib (Table I) is a third-generation inhibitor (13)(14)(15)(16). In addition, ensartinib, repotrectinib, and belizatinib are being investigated in ongoing clinical studies (17). It has been revealed that the median progression-free survival in patients using crizotinib was longer than that in patients undergoing chemotherapy in advanced ALK-positive lung cancer patients (12).…”

Section: Introductionmentioning

confidence: 99%

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Safety and efficacy of anaplastic lymphoma kinase tyrosine kinase inhibitors in non‑small cell lung cancer (Review)

Wang

2020

Oncol Rep

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Since the discovery of targeted therapy with epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) have been introduced as the first-line treatment for non-small cell lung cancer (NSCLC) patients who carry sensitizing ALK-activating mutations. Compared with conventional chemotherapeutic regimens, small-molecule ALK-TKIs exhibit excellent clinical efficacy in ALK-positive NSCLC. A series of studies have indicated that ALK-TKI agents as the first-line treatment, including crizotinib, ceritinib, brigatinib, alectinib and entrectinib, can benefit patients with ALK-positive NSCLC. However, resistance to ALK-TKIs has emerged. ALK-TKIs are associated with significantly disabling and undesirable effects that adversely impact quality of life and compliance. This study reviews the pharmacodynamics, efficacy and safety of ALK-TKI agents in order to summarize these effects as well as the relevant management strategies. It is worth emphasizing that the frequency and severity of an adverse effect often varies across different trials.

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Evolution in the treatment landscape of non-small cell lung cancer with ALK gene alterations: from the first- to third-generation of ALK inhibitors

Cited by 29 publications

References 88 publications

<p>Pharmacokinetic-Based Drug–Drug Interactions with Anaplastic Lymphoma Kinase Inhibitors: A Review</p>

<p>Pharmacokinetic-Based Drug–Drug Interactions with Anaplastic Lymphoma Kinase Inhibitors: A Review</p>

Characteristics and Clinical Outcomes of Non-small Cell Lung Cancer Patients in Korea With MET Exon 14 Skipping

Safety and efficacy of anaplastic lymphoma kinase tyrosine kinase inhibitors in non‑small cell lung cancer (Review)

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