COMPREHENSIVE MOLECULAR PROFILING OF LUNG ADENOCARCINOMA (The Cancer Genome Atlas Research Network, Nature 2014; 511: 543-550)
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In this study, molecular profiling of 230 resected lung adenocarcinomas was performed using mRNA, microRNA, and DNA sequencing integrated with copy number, methylation & proteomic analysis. 18 genes were significantly mutated, including RIT1 activating mutations & newly-described loss-of-functional MGA mutations. EGFR mutations were more frequent in females while RBM10 mutations were more common in males. Aberrations in NF1, MET, ERBB2 and RIT1 occurred in 13% of cases and were enriched in samples otherwise lacking an activated oncogene, suggesting a driver role for these events in certain tumours.
Summary: This study expands the range of targetable alterations in lung adenocarcinoma.
USING MULTIPLEXED ASSAYS OF ONCOGENIC DRIVERS IN LUNG CANCERS TO SELECT TARGETED DRUGS (Kris et al, JAMA 2014; 311: 1998-2006)
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733 patients with adenocarcinoma had genotyping testing for 10 specific genes. 466 (64%) had an identified oncogenic driver. The most common was KRAS (25%), sensitising EGFR (17%), ALK rearrangements (8%), other EGFR (4%), 2 or more genes (3%), and ERBB2/HER2 (3%). The results were used to select a targeted therapy in 28% of eligible patients & 44% of individuals with drivers received targeted therapy. Median survival was 3.5 years for those who received genotype-directed therapy, versus 2.4 years for those with an oncogenic driver who did not receive genotype-directed therapy.
Summary: Patients who received targeted therapies had improved survival but randomised controlled trials are needed.
CERITINIB IN ALK-REARRANGED NON-SMALL CELL LUNG CANCER (Shaw et al, NEJM 2014; 370: 1189-1197)
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In this phase 1 study, patients were given oral ceritinib (LDK378), a new ALK (anaplastic lymphoma kinase) inhibitor that has shown greater antitumor potency than crizotinib in preclinical studies. Ceritinib was highly active in patients with advanced, ALK-rearranged NSCLC, including those who had had disease progression during crizotinib treatment, regardless of the presence of resistance mutations in ALK.
Summary: Lung adenocarcinomas should be routinely tested for ALK rearrangements & in those who have disease progression crizotinib should be considered for ceritinib.