Treatment of intracranial disease in ALK positive lung cancer

ALK mutation is found in 2-7% of non-small cell lung cancers. The tyrosine kinase inhibitor (TKI) crizotinib is first line therapy but unfortunately has low blood brain barrier penetration and 40-50% of patients can develop brain metastasis while on crizotinib. The next generation of TKI theoretically have greater blood brain barrier penetration. Crinò et al (JCO,2016 vol. 34 no. 24 2866-2873) present the Novartis supported ASCEND-2 findings in which 140 patients from 51 centres were treated with ceritonib. The patients were performance status less than 2, ALK positive and had disease that had progressed despite both platinum based chemotherapy and crizotinib; 71% of subjects had brain metastasis, of which 72% had received radiotherapy. Analysis of a subgroup of 20 patients with active brain lesions showed an investigator assessed intracranial disease control rate (ICDR) of 80% (95% CI, 56.3% to 94.3%). Whole body response in the full analysis set gave a disease …