Analysis of EML4-ALK rearrangement in non-small cell lung cancer in Argentina

Verzura, María Alicia; Batagelj, Emilio; Bagnes, Claudia; Martín, Claudio; Enrico, Diego; Richardet, Eduardo; Iglesia, P de la

doi:10.1016/j.anndiagpath.2018.02.009

Cited by 4 publications

(5 citation statements)

References 19 publications

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“… 32 The mechanisms of relapse have been categorized as ALK-dependent and ALK-independent. 11 Generally, ALK-dependent resistance occurs as a result of secondary mutations within the target kinase that reinduce kinase activation, despite the presence of the TKI. 33 The emergence of secondary mutations hinder the binding of the TKI to the target kinase, and thus unchecked kinase activation ensues.…”

Section: Mechanisms Of Acquired Resistance To Crizotinibmentioning

confidence: 99%

“…7 Rearrangement in ALK-receptor tyrosine kinase, a molecular subtype of NSCLC, occurs in 5%−7% of NSCLC patients. [8][9][10][11] While in unselected NSCLC patients, overall frequency of ALK rearrangement is low, selection of patients based on clinicopathological features, such as no or light smoking history and adenocarcinoma histology results in higher frequencies (about 13%) of ALK-rearranged NSCLC. 16 There are an estimated 40,000 incident cases of ALKpositive NSCLC worldwide each year, and patient characteristics are quite dissimilar from the overall patient population with NSCLC.…”

Section: Introductionmentioning

confidence: 99%

“…16 There are an estimated 40,000 incident cases of ALKpositive NSCLC worldwide each year, and patient characteristics are quite dissimilar from the overall patient population with NSCLC. 11 ALK-positive NSCLC patients are generally younger (median age 52 years old), are never-to only light smokers, and primarily have adenocarcinoma histology. [12][13][14][15][16] Clinicopathological findings of younger age, never-to light smoking history and adenocarcinoma-predominant histology in ALK-positive patients were confirmed in a large real-world retrospective analysis recently.…”

Section: Introductionmentioning

confidence: 99%

“…Formation of the EML4–ALK fusion leads to activation, thereby potentiating proliferation and survival of the cancer cells. 11 , 23 Diagnosis is most typically made using fluorescence in situ hybridization (FISH), immunohistochemistry (IHC), or next-generation sequencing (NGS) of the tumor tissue. 24 , 25 In the US, FISH, IHC, and NGS are approved companion diagnostic tests to identify ALK-positive NSCLC.…”

Section: Introductionmentioning

confidence: 99%

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<p>Optimal Care for Patients with Anaplastic Lymphoma Kinase (ALK)–Positive Non–Small Cell Lung Cancer: A Review on the Role and Utility of ALK Inhibitors</p>

Singh

Chen

2020

CMAR

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The treatment of advanced non-small-cell lung cancer (NSCLC) has undergone a paradigm shift in the last decade. Molecular characterization of the disease has led to the rapid development of personalized medicine and swift delivery of targeted therapies to patients. The discovery of the anaplastic lymphoma kinase (ALK) gene in patients with NSCLC has resulted in rapid bench-bedside transition of several active drugs, with several others currently in clinical trials. After the first-generation ALK inhibitor crizotinib, nextgeneration ALK inhibitors have entered clinical applications for ALK-rearranged NSCLC. Ceritinib, alectinib, and brigatinib have all received approval for ALK-positive patients who have failed prior crizotinib, as well as first-line therapy in treatment-naïve patients based on favorable efficacy. Most recently, lorlatinib, a potent, newer-generation ALK inhibitor, has been approved as second-or third-line treatment. These advances have led to better patient outcomes, but concurrently have led to several crucial unanswered questions about optimal care for ALK-positive NSCLC patients. The ultimate acquisition of resistance to ALKinhibitor therapy poses a challenge to ongoing research efforts, in addition to the routine management of these patients in the clinic. This review provides a summary of the clinical development of crizotinib, ceritinib, alectinib, brigatinib, and lorlatinib and highlights current management paradigms, current and evolving clinical information, emerging clinical decision-making and sequencing of therapy in advanced, metastatic, or recurrent ALK-positive NSCLC.

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Section: Mechanisms Of Acquired Resistance To Crizotinibmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

<p>Optimal Care for Patients with Anaplastic Lymphoma Kinase (ALK)–Positive Non–Small Cell Lung Cancer: A Review on the Role and Utility of ALK Inhibitors</p>

Singh

Chen

2020

CMAR

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“…Since the discovery of oncogenic driver mutations and the availability of molecular targeted therapy, the management paradigm for patients with NSCLC has drastically changed in the past decade. Genomic rearrangement in anaplastic lymphoma kinase ( ALK ) receptor tyrosine kinase, a specific molecular subtype of NSCLC, occurs in 5%−7% of patients with NSCLC (6-8). However, due to the large population of patients with NSCLC, the absolute number of ALK -positive NSCLC patients is astonishing, with an estimated 40,000 cases occurring worldwide each year (9).…”

Section: Introductionmentioning

confidence: 99%

Sequential therapy according to distinct disease progression patterns in advanced ALK-positive non-small-cell lung cancer after crizotinib treatment

Xu¹,

Gao

et al. 2019

Chinese Journal of Cancer Research

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Objective Crizotinib is recommended as the first-line therapy for advanced anaplastic lymphoma kinase ( ALK )-positive non-small-cell lung cancer (NSCLC). Despite its initial efficacy, patients ultimately acquire resistance to crizotinib within 1 year. In such patients, the optimal sequential therapy after crizotinib treatment remains unknown. This study explored which sequential therapy option confers the greatest benefit. Methods A total of 138 patients with advanced ALK -positive NSCLC resistant to crizotinib were studied. Based on patterns of disease progression of metastases, patients were divided into 3 groups: brain progression, non-liver progression, and liver progression. Sequential therapies included crizotinib continuation plus local therapy, next-generation ALK inhibitors (ALKi’s), and chemotherapy. The primary endpoint was overall survival (OS) from the time of crizotinib resistance to death or last follow-up. Results The 138 patients included 64 cases with progression in brain, 57 cases in non-liver sites and 17 cases in liver. A significant difference in OS was observed among the distinct progression pattern (median OS, 25.4 months in brain, 15.8 months in non-liver, and 10.8 months in liver, respectively, P=0.020). The difference in OS among sequential therapies was statistically significant in the non-liver progression group (median OS, 27.6 months with next-generation ALKi’s, 13.3 months with crizotinib continuation, and 10.8 months with chemotherapy, respectively, P=0.019). However, crizotinib continuation plus local therapy seems to provide non-inferior median OS compared with next-generation ALKi’s for patients with brain progression (median OS, 28.9 months vs . 32.8 months, P=0.204). And no significant differences in OS were found in patients with progression in liver (P=0.061). Conclusions Crizotinib continuation together with local therapy might be a feasible strategy for patients with progression in brain beyond crizotinib resistance, as well as next-generation ALKi’s. Next-generation ALKi’s tended to provide a survival benefit in patients with non-liver progression.

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ALK rearrangements: Biology, detection and opportunities of therapy in non-small cell lung cancer

Rosas

Ruiz

Araujo

et al. 2019

Critical Reviews in Oncology/Hematology

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Analysis of EML4-ALK rearrangement in non-small cell lung cancer in Argentina

Cited by 4 publications

References 19 publications

<p>Optimal Care for Patients with Anaplastic Lymphoma Kinase (ALK)–Positive Non–Small Cell Lung Cancer: A Review on the Role and Utility of ALK Inhibitors</p>

<p>Optimal Care for Patients with Anaplastic Lymphoma Kinase (ALK)–Positive Non–Small Cell Lung Cancer: A Review on the Role and Utility of ALK Inhibitors</p>

Sequential therapy according to distinct disease progression patterns in advanced ALK-positive non-small-cell lung cancer after crizotinib treatment

ALK rearrangements: Biology, detection and opportunities of therapy in non-small cell lung cancer

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