Prevalence and natural history of ALK positive non-small-cell lung cancer and the clinical impact of targeted therapy with ALK inhibitors

Chia, Puey Ling; Mitchell, Paul; Dobrovic, Alexander; John, Thomas

doi:10.2147/clep.s69718

Cited by 150 publications

(116 citation statements)

References 97 publications

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“…However, NSCLC is not one single entity, in fact, it is subdivided into adenocarcinoma also known as lung adenocarcinoma (AC and LUAD respectively, 40% of all NSCLCs), lung squamous cell carcinoma (or LUSC, 20%-30% of all NSCLCs ), large cell carcinoma (2%-5% of all NSCLCs) or not otherwise specified (20% of all NSCLCs), according to the histological type [ Figure 1]; and in wild-type (without any known mutation) or mutated ("oncogene addicted"), if a mutation is present. Presently, we are only able to specifically target oncogenic mutations in the adenocarcinoma histological type, most notably epidermal growth factor receptor (EGFR, 15%-20% of all AC NSCLC) and ALK (4%-6% of all AC NSCLC, mainly younger and non smokers/light smokers patients) [1][2][3][4][5][6] .…”

Section: Nsclc Epidemiologymentioning

confidence: 99%

Personalized genomic medicine: non-small-cell lung cancer and anaplastic lymphoma kinase

Malapelle¹,

Gravara²,

Battiloro³

et al. 2019

JTGG

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Genomic medicine, that is to say, using genomic information about a patient in order to set the diagnostic path and to tailor therapy to his/her specific characteristics, is one of the cornerstones of modern precision medicine and forms an integral part of several fields, oncology first of all. Lung cancer is the leading cause of cancer mortality, causing more than 1.6 million deaths worldwide per year and non-small-cell lung cancer (NSCLC) accounts for approximately 85% of lung cancers. In a small subset of NSCLC (5%-8%), we can detect a genomic rearrangement on chromosome 2, between the Echinoderm microtubule-associated protein-like 4 (EML4) gene and the anaplastic lymphoma kinase (ALK) gene, resulting in the chimeric protein EML4-ALK, that acts as an oncogene and that can be specifically targeted by an ALKtyrosine kinase inhibitor (TKI) therapy. However, a major clinical challenge is represented by the fact that, after a first line ALK-TKI treatment, patients eventually develop acquired resistance to these agents, opening new scenarios for the right second-line drug choice.

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Section: Nsclc Epidemiologymentioning

confidence: 99%

Personalized genomic medicine: non-small-cell lung cancer and anaplastic lymphoma kinase

Malapelle¹,

Gravara²,

Battiloro³

et al. 2019

JTGG

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“…The anaplastic lymphoma kinase ( ALK ) gene is frequently involved in translocations that lead to gene fusions in a variety of malignancies, including lung cancer. It is estimated that ALK gene rearrangements occur in 4–5% of all patients with advanced non‐small‐cell lung cancer (NSCLC) …”

mentioning

confidence: 99%

Pharmacologic study (JP28927) of alectinib in Japanese patients with ALK+ non‐small‐cell lung cancer with or without prior crizotinib therapy

et al. 2016

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We report pharmacokinetics, efficacy and safety data for a new 150‐mg alectinib capsule in ALK+ non‐small‐cell lung cancer in a multicenter, open‐label pharmacologic study (JP28927). Eligible patients (≥20 years, locally advanced/metastatic ALK+ disease, ALK inhibitor‐naïve and ‐pretreated [including crizotinib refractory]) were randomized 1:1 to receive one of two sequences of alectinib 300 mg twice daily (comprising different schedules of 20/40‐mg and 150‐mg capsules) until investigator‐determined lack of clinical benefit. Co‐primary endpoints were: bioequivalence of alectinib 20/40 mg vs 150 mg; food effect with 150 mg; and safety. Thirty‐five patients were enrolled; median treatment duration was 13.1 months (range 1.1−15.0). Under fasting conditions, exposure of the two formulations was similar; mean AUC last ± standard deviation 3230 ± 914 h·ng/mL vs 3710 ± 1040 h·ng/mL, respectively, for 150‐mg vs 20/40‐mg capsules. Food effect with 150 mg alectinib was negligible. Treatment‐related adverse events in >20% of patients were constipation (31.4%), dysgeusia (25.7%), and decreased white blood cell and neutrophil count (22.9% each). No treatment‐related grade 4/5 events occurred. Median time to response was 1.2 months (95% CI 1.1−2.1). For the full analysis set (n = 35) and crizotinib‐failure subpopulations (n = 23), the overall response rate was 70.0% (95% CI 50.6−85.3) and 65.0% (95% CI 40.8−84.6), and median progression‐free survival was 13.9 months (95% CI 11.1−not reached) and 12.9 months (95% CI 3.9−not reached), respectively. The 150‐mg capsule had a similar exposure profile to 20/40‐mg capsules. Alectinib demonstrated promising efficacy and was well tolerated.

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“…If we consider females and males combined the average age is 61-56 years despite that is 5-8 years higher like in other studies. Analysis of only the non-smoker and young patients from the ALK rearrangement point of view frequency showed up to 17% [28,31,32]. In our study, the positive results were higher (25%) in the female patients with lung adenocarcinoma.…”

Section: Resultsmentioning

confidence: 41%

Anaplastic Lymphoma Kinase (ALK) Overexpression in Lung Cancer Biopsies - An 18 month study in north western Romania

Pop¹,

Pusta²,

Buhaş³

et al. 2019

Rev. Chim.

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Lung cancer is the first cause of death worldwide of oncological patients. Most of them are non-small cell lung cancer (NSCLC) and many of them are characterized by different molecular markers that allow the development of personalized treatments. Epithelial growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) are the most frequently tested genes in lung adenocarcinoma and other lung carcinomas with glandular component. The aim of our study is to evaluate the distribution of ALK gene mutation in lung cancer patient from North West part of Romania. We analysed a number of 289 lung biopsies along 18 months. The samples have been incubated with monoclonal ALK antibodies (clone D5F3), according to the manufacturer�s instruction. The interpretation guide provided by manufacturer was used to distinguish the positives vs negative cases. In our study from a total number of 289 lung biopsies, 196 cases were carcinomas. 57.65 % from the total number of lung cancers were adenocarcinomas. A total number of 79 cases have been analysed for ALK gene supra expression. 5.08 % of adenocarcinomas were positive for ALK, but the mean age for this population is higher comparing with the data from other studies.

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Prevalence and natural history of ALK positive non-small-cell lung cancer and the clinical impact of targeted therapy with ALK inhibitors

Cited by 150 publications

References 97 publications

Personalized genomic medicine: non-small-cell lung cancer and anaplastic lymphoma kinase

Personalized genomic medicine: non-small-cell lung cancer and anaplastic lymphoma kinase

Pharmacologic study (JP28927) of alectinib in Japanese patients with ALK+ non‐small‐cell lung cancer with or without prior crizotinib therapy

Anaplastic Lymphoma Kinase (ALK) Overexpression in Lung Cancer Biopsies - An 18 month study in north western Romania

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