Bénédicte Mastroianni

Immunohistochemistry evaluation of biomarker expression in non-small cell lung cancer (Pharmacogenoscan study)

OBJECTIVES Platinum-based chemotherapy regimens are the standard treatment of non-small cell lung cancer (NSCLC). In this study, our objective was to identify tumor tissue protein biomarkers that might predict a benefit from these treatments. MATERIALS AND METHODS The Pharmacogenoscan study prospectively included consecutive chemotherapy-naive NSCLC patients at any stage between 2005 and 2010 at six hospitals in the Rhône-Alpes-Auvergne region of France. Of the 537 patients in the full analysis set, 460 had a complete histological diagnosis. We used the tumor tissue samples for an immunohistochemical evaluation of eight biomarkers: ERCC1, BRCA1, p53, p27kip1, class III β-tubulin (TUBB3), Bax, Fas, and FasL. We looked for associations between these biomarkers and the disease control rate (DCR) after 2/3 cycles of platinum-based chemotherapy, progression-free survival (PFS), and overall survival (OS). RESULTS A tissue sample adequate for testing at least one biomarker was available for 289 patients. We found no significant association between biomarker expression levels and clinical or pathological variables; TUBB3 showed a trend toward higher expression in adenocarcinomas (P=0.005). For none of the biomarkers were significant associations found between expression level and DCR, PFS, or OS. TUBB3-negative and FasL-negative tumors showed associations of borderline significance with higher DCR. CONCLUSION In a large cohort of patients with predominantly advanced or metastatic NSCLC, none of eight tested immunohistochemical biomarkers predicted the chemotherapy response or survival. Our data indicate limited usefulness of protein biomarkers in metastatic NSCLC and a need for further research based on molecular signatures of greater complexity.

Characteristics and Outcomes of Patients with Lung Cancer Harboring Multiple Molecular Alterations: Results from the IFCT Study Biomarkers France

Introduction: Little is known about the prevalence, prognosis, and response to treatment of advanced NSCLC harboring multiple genomic alterations. Methods: The French Biomarkers France database, which includes 17,664 patients, was used. The prevalence of multiple alterations, their associations, their impact on prognosis (overall survival [OS]), and their response to targeted or conventional treatments (progression‐free survival [PFS] and objective response rate) were assessed and compared with those of patients harboring single or no mutation. Results: We identified 162 patients (0.9%) with double alterations and three with triple mutations. Multiple molecular alterations preferentially involved KRAS (67.3%), phosphatidylinositol‐4,5‐bisphosphate 3‐kinase catalytic subunit alpha gene (PIK3CA) (53.3%), and EGFR (42.4%). Patients with multiple alterations were more likely to be male (56.4%), be never‐smokers (25.8 versus 34.7%, p < 0.001), and exhibit adenocarcinomas (83.6%). OS did not differ between single and multiple alterations. Patients with EGFR/KRAS and EGFR/PIK3CA mutations experienced worse PFS than did patients with only EGFR mutations (7.1 and 7.1 versus 14.9 months, p = 0.02 and 0.002, respectively). Concomitant mutations in patients harboring anaplastic lymphoma receptor tyrosine kinase gene (ALK) rearrangement bore little impact on OS (17.7 versus 20.3 months, p = 0.57) or PFS (10.3 versus 12.1 months, p = 0.93). Patients harboring KRAS mutations plus another alteration had an OS time (13.4 versus 11.2 months, p = 0.28), PFS time (6.4 versus 7.2 months, p = 0.78), and objective response rate under first‐line chemotherapy (41.7% versus 37.2%) similar to those of patients harboring KRAS mutations only. Conclusions: With almost 1% of patients harboring multiple alterations, the dogma of mutually exclusive mutations should be reconsidered. Although double mutations do not decrease OS, they do alter PFS under first‐line treatment for patients with EGFR mutations. Among limited numbers of patients, therapies targeting the dominant oncogene seem to usually remain active.

Assessment of palliative care for advanced non-small-cell lung cancer in France: A prospective observational multicenter study (GFPC 0804 study)

INTRODUCTION Few studies assessed, in real life, symptoms, specific interventions and factors influencing palliative care (PC) initiation for patients with advanced non-small-cell lung cancer (NSCLC). The objective of this study was to examine, in a prospective cohort of advanced NSCLC patients, PC use and factors associated with early (≤3 months after diagnosis) PC initiation. METHODS It was an observational multicenter study. Each center included 10 consecutive patients with PC initiation. RESULTS 514 patients were enrolled by 39 centers (age: 62.3 ± 10.7 years, performance status: 0/1; 68.6% cases). At baseline, the most frequent symptoms concerned pain (43.6%), malnutrition (37%) and psychological disorders (25.3%). Specific interventions were infrequent for pain control and malnutrition, but were more numerous for psychological and social problems and terminal care. Median time between diagnosis and PC initiation was 35 [13-84] days, median PC duration was 4.2 [0.6-9.3] months. Median overall survival was 8.6 [6.6-10.7] months; median survival after PC initiation was 3.6 [3.2-4.5] months. In multivariate analysis, only PS ≥2 was linked to early PC. CONCLUSION This study showed that early PC initiation is not a standard for patients with advanced NSCLC.

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

Characteristics of Lung Cancer in Patients Younger than 40 Years: A Prospective Multicenter Analysis in France

Objectives: The aim of this study was to describe the demographic and clinico-pathological characteristics of lung cancer in patients younger than 40 years. Materials and Methods: This was a prospective study performed within the Groupe Français de Pneumo-Cancérologie. Consecutive patients diagnosed with lung cancer before the age of 40 years were eligible. Data on demographics, medical history, clinico-pathological characteristics, treatment and overall survival were analysed. Results: In total, 146 patients were included from January 2011 to December 2013. Median age was 38 years (IQR: 34–40). Women accounted for 41%. Main histological type was adenocarcinoma (77%). Only 3% had a prior history of cancer, but a family history (first- or second-degree relatives) of cancer was reported in 80 (55%) patients; 85 and 50% were current or past smokers of tobacco and cannabis, respectively; 82% had stage IIIB/IV at diagnosis. Median overall survival was 15.3 (95% CI: 8.1–24.0) months in the whole population, 10.3 (95% CI: 12.5–14.2) months in stage IV and 15 (95% CI: 8.7–35.2) months in stage III. One- and two-year overall survival rates were 57% (95 CI: 49–65) and 31.5% (95 CI: 27–43), respectively. Compared to smokers, non-smokers were significantly younger and more often females. Median overall survival was not statistically different between smokers and non-smokers.