Therapeutic management of ALK+ nonsmall cell lung cancer patients.
With therapeutic approaches based on oncogene addiction offering significant anticancer benefit, the identification of anaplastic lymphoma kinase (ALK) rearrangements is a key aspect of the management of lung cancers. The EML4-ALK gene fusion is detected in 4-8% of all lung cancers, predominantly in light smokers or nonsmokers. Crizotinib, the first agent to be approved in this indication, is associated with a median progression-free survival of 10.9 months when given as first-line treatment and 7.7 months when administered after chemotherapy. Median overall survival with crizotinib in the second-line setting is 20.3 months. Second-generation ALK inhibitors are currently being evaluated, with early studies giving impressive results, notably in patients resistant to crizotinib or with brain metastases. Among available chemotherapies, pemetrexed appears to be particularly active in this population. Despite this progress, several questions remain unanswered. What detection strategies should be favoured? What underlies the mechanisms of resistance and what options are available to overcome them? What are the best approaches for progressing patients? This review provides an overview of current data in the literature and addresses these questions.
Dept of Medical Oncology, Hopital Avicenne, Bobigny, France Paris 13 University, Paris, France.
Boris
B
Duchemann
Dept of Medicine, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA.
Luc
L
Friboulet
Dept of Cancer Medicine, Gustave Roussy, Villejuif, France Paris-Sud University, Paris, France benjamin.besse@gustaveroussy.fr.
Benjamin
B
Besse
D000077548:Anaplastic Lymphoma Kinase; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000473:pathology; D002227:Carbazoles / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics*; D002986:Clinical Trials as Topic; D000077547:Crizotinib; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D009362:Neoplasm Metastasis; D010880:Piperidines / Q000627:therapeutic use; D011237:Predictive Value of Tests; D011379:Prognosis; D011720:Pyrazoles / Q000627:therapeutic use; D011725:Pyridines / Q000627:therapeutic use; D011743:Pyrimidines / Q000627:therapeutic use; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics*; D012907:Smoking; D013450:Sulfones / Q000627:therapeutic use
D000970:Antineoplastic Agents; D002227:Carbazoles; D010880:Piperidines; D011720:Pyrazoles; D011725:Pyridines; D011743:Pyrimidines; D013450:Sulfones; D000077547:Crizotinib; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases; C586847:ceritinib; C582670:alectinib