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01.03.2013 | Review

ALK inhibitors: a new targeted therapy in the treatment of advanced NSCLC

verfasst von: Francesca Casaluce, Assunta Sgambato, Paolo Maione, Antonio Rossi, Carmine Ferrara, Alba Napolitano, Giovanni Palazzolo, Fortunato Ciardiello, Cesare Gridelli

Erschienen in: Targeted Oncology | Ausgabe 1/2013

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Abstract

The anaplastic lymphoma kinase (ALK) fusion gene is a key oncogenic driver in a subset of patients with advanced non-small cell lung cancer (NSCLC). Oncogenic fusion genes, including echinoderm microtubule-associated protein-like 4 (EML4) and ALK, have been detected in approximately 2–7 % of NSCLC patients. Fluorescence in situ hybridization (FISH) is the recommended method for detecting ALK gene rearrangement. EML4–ALK fusion genes define a molecular subset of NSCLC with distinct clinical characteristic (lung adenocarcinoma, never or former smoker, usually mutually exclusive with EGFR mutations). Crizotinib (PF-02341066) is an orally bioavailable, ATP-competitive, small molecule inhibitor of both the receptor tyrosine kinases ALK and c-MET (hepatocyte growth factor receptor). Crizotinib has been shown to yield important clinical benefit such as objective response rate, progression-free survival (PFS), and anticipated improvements in quality of life when used in pretreated patients with advanced NSCLC harboring EML4–ALK gene rearrangement. Preliminary phase II data suggested that crizotinib is safe and well tolerated with rapid and robust antitumor activity. A phase III randomized trial in a second-line setting showed response rate and PFS (primary study endpoint) advantage for crizotinib as compared to second-line chemotherapy. Treatment-related adverse events, predominantly restricted to the gastrointestinal and visual systems, are generally self-limiting or easily managed. Crizotinib is a new standard of care for patients with advanced, ALK-positive, NSCLC. In this review, we will discuss the discovery of ALK rearrangements, the clinical epidemiology of lung cancer driven by ALK, the clinical data for ALK-targeted therapy in NSCLC, and ongoing ALK inhibitor-based clinical trials.

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Titel: ALK inhibitors: a new targeted therapy in the treatment of advanced NSCLC
verfasst von: Francesca Casaluce
Assunta Sgambato
Paolo Maione
Antonio Rossi
Carmine Ferrara
Alba Napolitano
Giovanni Palazzolo
Fortunato Ciardiello
Cesare Gridelli
Publikationsdatum: 01.03.2013
Verlag: Springer-Verlag
Erschienen in: Targeted Oncology / Ausgabe 1/2013
Print ISSN: 1776-2596
Elektronische ISSN: 1776-260X
DOI: https://doi.org/10.1007/s11523-012-0250-9

Springer Medizin

ALK inhibitors: a new targeted therapy in the treatment of advanced NSCLC

Abstract

Neu im Fachgebiet Onkologie

Adjuvante Immuntherapie verlängert Leben bei RCC

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

Bei Senioren mit Prostatakarzinom auf Anämie achten!

ICI-Therapie in der Schwangerschaft wird gut toleriert

Update Onkologie

Springer Medizin

Abstract

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