This is the first trial to directly compare efficacy and safety of alectinib versus standard chemotherapy in advanced/metastatic anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer (NSCLC) patients who have progressed on, or were intolerant to, crizotinib. ALUR (MO29750; NCT02604342) was a randomized, multicenter, open-label, phase III trial of alectinib versus chemotherapy in advanced/metastatic ALK-positive NSCLC patients previously treated with platinum-based doublet chemotherapy and crizotinib. Patients were randomized 2 : 1 to receive alectinib 600 mg twice daily or chemotherapy (pemetrexed 500 mg/m² or docetaxel 75 mg/m², both every 3 weeks) until disease progression, death, or withdrawal. Primary end point was investigator-assessed progression-free survival (PFS). Altogether, 107 patients were randomized (alectinib, n = 72; chemotherapy, n = 35) in 13 countries across Europe and Asia. Median investigator-assessed PFS was 9.6 months [95% confidence interval (CI): 6.9–12.2] with alectinib and 1.4 months (95% CI: 1.3–1.6) with chemotherapy [hazard ratio (HR) 0.15 (95% CI: 0.08–0.29); P < 0.001]. Independent Review Committee-assessed PFS was also significantly longer with alectinib [HR 0.32 (95% CI: 0.17–0.59); median PFS was 7.1 months (95% CI: 6.3–10.8) with alectinib and 1.6 months (95% CI: 1.3–4.1) with chemotherapy]. In patients with measurable baseline central nervous system (CNS) disease (alectinib, n = 24; chemotherapy, n = 16), CNS objective response rate was significantly higher with alectinib (54.2%) versus chemotherapy (0%; P < 0.001). Grade ≥3 adverse events were more common with chemotherapy (41.2%) than alectinib (27.1%). Incidence of AEs leading to study-drug discontinuation was lower with alectinib (5.7%) than chemotherapy (8.8%), despite alectinib treatment duration being longer (20.1 weeks versus 6.0 weeks). Alectinib significantly improved systemic and CNS efficacy versus chemotherapy for crizotinib-pretreated ALK-positive NSCLC patients, with a favorable safety profile. ClinicalTrials.gov NCT02604342; Roche study MO29750

Purpose: Lung squamous cell carcinoma (SCC) is the second most prevalent type of lung cancer. Currently, no targeted therapeutics are approved for treatment of this cancer, largely because of a lack of systematic understanding of the molecular pathogenesis of the disease. To identify therapeutic targets and perform comparative analyses of lung SCC, we probed somatic genome alterations of lung SCC by using samples from Korean patients.Patients and Methods: We performed whole-exome sequencing of DNA from 104 lung SCC samples from Korean patients and matched normal DNA. In addition, copy-number analysis and transcriptome analysis were conducted for a subset of these samples. Clinical association with cancer-specific somatic alterations was investigated.Results: This cancer cohort is characterized by a high mutational burden with an average of 261 somatic exonic mutations per tumor and a mutational spectrum showing a signature of exposure to cigarette smoke. Seven genes demonstrated statistical enrichment for mutation: TP53, RB1, PTEN, NFE2L2, KEAP1, MLL2, and PIK3CA). Comparative analysis between Korean and North American lung SCC samples demonstrated a similar spectrum of alterations in these two populations in contrast to the differences seen in lung adenocarcinoma. We also uncovered recurrent occurrence of therapeutically actionable FGFR3-TACC3 fusion in lung SCC.Conclusion: These findings provide new steps toward the identification of genomic target candidates for precision medicine in lung SCC, a disease with significant unmet medical needs.

Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites. Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients. We apply novel mixed model methodology (GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cancers, and the genetic correlation between pairs of cancers. GWAS heritability was statistically significant at nearly all sites, with the estimates of array-based heritability, hl (2), on the liability threshold (LT) scale ranging from 0.05 to 0.38. Estimating the combined heritability of multiple smoking characteristics, we calculate that at least 24% (95% confidence interval [CI] = 14% to 37%) and 7% (95% CI = 4% to 11%) of the heritability for lung and bladder cancer, respectively, can be attributed to genetic determinants of smoking. Most pairs of cancers studied did not show evidence of strong genetic correlation. We found only four pairs of cancers with marginally statistically significant correlations, specifically kidney and testes (ρ = 0.73, SE = 0.28), diffuse large B-cell lymphoma (DLBCL) and pediatric osteosarcoma (ρ = 0.53, SE = 0.21), DLBCL and chronic lymphocytic leukemia (CLL) (ρ = 0.51, SE =0.18), and bladder and lung (ρ = 0.35, SE = 0.14). Correlation analysis also indicates that the genetic architecture of lung cancer differs between a smoking population of European ancestry and a nonsmoking Asian population, allowing for the possibility that the genetic etiology for the same disease can vary by population and environmental exposures. Our results provide important insights into the genetic architecture of cancers and suggest new avenues for investigation.

Background: Pulmonary actinomycosis is a chronic pulmonary infection caused by Actinomyces. Both improving oral hygiene and early application of antibiotics to the case of suspicious pulmonary infections result in changes in incidences and presentations of pulmonary actinomycosis. However, there are little reports dealt with the recent clinical characteristics of pulmonary actinomycosis. This study aimed to review the characteristics of pulmonary actinomycosis occurred during the first decade of 21st century. Methods: This retrospective study was performed on 94 subjects with pulmonary actinomycosis diagnosed pathologically from January 2000 to December 2010 in 13 hospitals in Korea. Results: The data of the study showed that pulmonary actinomycosis occurs frequently in middle to old-aged males (mean age; 57.7 years old) and that the most common symptoms are cough, hemoptysis, and sputum production. Various radiologic features such as the consolidation with central low attenuation (74.5%) and no regional predominance were also observed. Most of patients recovered completely with medical and/or surgical treatment, reaching approximately 98% cure rate. Conclusions: The results demonstrate that pulmonary actinomycosis is one of the cautious pulmonary diseases. More importantly, in cases of persistent hemoptysis or for differential diagnosis from lung malignancy, our data have revealed that surgical resection appears to be a useful intervention and that radiologic diagnosis may not provide decisive information. These findings indicate that it is important for the clinicians to include pulmonary actinomycosis as one of differential diagnoses for refractory pulmonary abnormal lesions to the current usual management.