Patrick Dumont

No impact of passive smoke on the somatic profile of lung cancers in never-smokers

EGFR and HER2 mutations and ALK rearrangement are known to be related to lung cancer in never-smokers, while KRAS, BRAF and PIK3CA mutations are typically observed among smokers. There is still debate surrounding whether never-smokers exposed to passive smoke exhibit a “smoker-like” somatic profile compared with unexposed never-smokers. Passive smoke exposure was assessed in the French BioCAST/IFCT-1002 never-smoker lung cancer cohort and routine molecular profiles analyses were compiled. Of the 384 patients recruited into BioCAST, 319 were tested for at least one biomarker and provided data relating to passive smoking. Overall, 219 (66%) reported having been exposed to passive smoking. No significant difference was observed between mutation frequency and passive smoke exposure (EGFR mutation: 46% in never exposed versus 41% in ever exposed; KRAS: 7% versus 7%; ALK: 13% versus 11%; HER2: 4% versus 5%; BRAF: 6% versus 5%; PIK3CA: 4% versus 2%). We observed a nonsignificant trend for a negative association between EGFR mutation and cumulative duration of passive smoke exposure. No association was found for other biomarkers. There is no clear association between passive smoke exposure and somatic profile in lifelong, never-smoker lung cancer. Never-smokers with lung cancer exposed to passive smoke do not have a smoker-like somatic mutation profile http://ow.ly/Eheoi

The new face of non-small-cell lung cancer in men: Results of two French prospective epidemiological studies conducted 10 years apart

OBJECTIVES To evaluate the impact of epidemiological changes observed in 10 years in men with NSCLC on 1-year mortality; to compare prognosis factors of 1-year mortality according to gender. MATERIAL AND METHODS The French College of General Hospital Respiratory Physicians conducted two prospective epidemiological multicentre studies at a 10-year interval (KBP-2000-CPHG and KBP-2010-CPHG). These studies included all adult patients with primary lung cancer histologically or cytologically diagnosed between 1(st) January and 31(st) December for the years 2000 and 2010, managed in the pneumology department of the participating hospitals. A standardised form was completed for each patient. A steering committee checked recruitment exhaustiveness. Vital status 1 year after diagnosis was collected. RESULTS In 2000 and 2010 respectively, 137 and 104 centres included 3921 and 4597 men and 748 and 1486 women with NSCLC. In 2010 compared to 2000, male patients were older but had better performance status (PS); they were less frequently ever-smokers and heavy smokers; their cancer (usually diagnosed at advanced stage) was more often adenocarcinoma (p<0.0001). In 10 years, 1-year mortality has significantly decreased in men (from 61.2% to 56.6%, p<0.0001) and in women (from 58.1% to 50.9%, p<0.0001), but remained higher in men than in women leading to increased difference between men and women. Decreased 1-year mortality remained statistically significant after adjustment on age, PS, smoking, and histology (men: OR=0.81, 95% CI=0.73-0.90, p<0.0001; women: 0.71, 0.57-0.88, p<0.002). Active smoking was not a prognosis factor in men (OR=1.04, CI=0.79-1.37, p=0.78); age (>75 years) had less impact on mortality in men than in women (men: OR=1.43, CI=1.22-1.67, p ≤ 0.0001; women: OR=2.32, CI=1.71-3.15; p<0.0001). CONCLUSIONS The improved 1-year survival in 2010 as compared with 2000 was independent of age, smoking, PS, and histology, suggesting that it reflected new treatment and strategy efficacy. One-year mortality remains higher in men than in women.

Association between lung cancer somatic mutations and occupational exposure in never-smokers.

Occupational exposure constitutes a common risk factor for lung cancer. We observed molecular alterations in 73% of never-smokers, 35% of men and 8% of women were exposed to at least one occupational carcinogen. We report herein associations between molecular patterns and occupational exposure. BioCAST was a cohort study of lung cancer in never-smokers that reported risk factor exposure and molecular patterns. Occupational exposure was assessed via a validated 71-item questionnaire. Patients were categorised into groups that were unexposed and exposed to polycyclic aromatic hydrocarbons (PAH), asbestos, silica, diesel exhaust fumes (DEF), chrome and paints. Test results were recorded for EGFR, KRAS, HER2, BRAF and PIK3 mutations, and ALK alterations. Overall, 313 out of 384 patients included in BioCAST were analysed. Asbestos-exposed patients displayed a significantly lower rate of EGFR mutations (20% versus 44%, p=0.033), and a higher rate of HER2 mutations (18% versus 4%, p=0.084). ALK alterations were not associated with any occupational carcinogens. The DEF-exposed patients were diagnosed with a BRAF mutation in 25% of all cases. Chrome-exposed patients exhibited enhanced HER2 and PIK3 mutation frequency. Given its minimal effects in the subgroups, we conclude that occupational exposure slightly affects the molecular pattern of lung cancers in never-smokers. In particular, asbestos-exposed patients have a lower chance of EGFR mutations. Asbestos exposure is associated with a lower rate of EGFR mutation in lung cancer of never-smokers http://ow.ly/wFUY30fkbcz

Phase II study assessing the benefit of cisplatin re-introduction (stop-and-go strategy) in patients with advanced non-squamous non-small cell lung cancer: the IFCT-1102 BUCiL study (a Better Use of Cisplatin in Lung cancer)

Introduction This single-arm phase II trial aimed to evaluate a stop-and-go strategy with cisplatin-based chemotherapy and bevacizumab in advanced non-squamous non-small cell lung cancer (NSCLC). Methods Patients were initially treated with three cycles of pemetrexed, cisplatin plus bevacizumab (sequence 1) followed by bevacizumab maintenance and after progression, re-introduction of three cycles of pemetrexed, cisplatin plus bevacizumab (sequence 2) and pemetrexed plus bevacizumab maintenance. The primary endpoint was the proportion of patients with advanced non-squamous NSCLC receiving the complete sequence 2 without platinum dose reduction (hypothesis ≥75%). Results 120 patients with performance status ≤1 were included. Of 113 patients evaluable for efficacy, 65 (57.5%) entered in sequence 2 and 56 (86%) received the three planned cycles including 37 (56.9%, 95% CI 45.1 to 73.6) without platinum dose reduction. The median progression-free survival 1 (PFS1; inclusion to progression 1) was 5.6 months (95% CI 5.0 to 6.3) and median PFS2 (progression 1 to progression 2) was 6.8 months (95% CI 5.8 to 8.8). The median disease control duration (PFS1+PFS2; n=65) was 12.4 months (95% CI 11.2 to 14.9). The median overall survival was 17.7 months (95% CI 13.1 to 21.6) and 20.5 months (95% CI 16.9 to 26.9) for patients reaching the sequence 2 (n=65). Conclusion Although the stringent primary endpoint was not met, this stop-and-go strategy with platinum-based chemotherapy plus bevacizumab continuation beyond progression compares favourably with standard schedule, deserving to be further studied in advanced non-squamous NSCLC.