BRCA1, LMO4, and CtIP mRNA Expression in Erlotinib-Treated Non–Small-Cell Lung Cancer Patients with EGFR Mutations

IntroductionLung adenocarcinoma patients harboring EGFR activating mutations attain improved progression-free survival (PFS) with treatment with epidermal growth factor receptor tyrosine kinase inhibitors. However, patients ultimately relapse, indicating that other genetic factors could influence outcome in such patients. We hypothesized that PFS could be influenced by the expression of genes in DNA repair pathways.MethodsWe examined the mRNA expression of C terminus-binding protein–interacting protein and Lin11, Isl-1, and Mec-3 domain only 4 (LMO4) in pretreatment tumor samples from 91 erlotinib-treated advanced non–small-cell lung cancer patients with EGFR mutations in whom breast cancer gene 1 (BRCA1) expression and the concomitant presence of the EGFR T790M mutation had previously been assessed. Gene expression was analyzed by polymerase chain reaction, using β-actin as endogenous gene. Results were correlated with PFS and overall survival.ResultsIn patients with low LMO4 levels, PFS was 13 months, whereas it was not reached for those with high LMO4 levels (p = 0.03). In patients with low levels of both BRCA1 and LMO4, PFS was 19 months whereas it was not reached in those with low BRCA1 and high LMO4 mRNA levels (p = 0.04). In patients with high BRCA1 and low LMO4 levels, PFS was 8 months, whereas it was 18 months in those with high levels of both genes (p = 0.03).ConclusionsLow BRCA1 and high LMO4 levels were associated with longer PFS to erlotinib. Baseline assessment of BRCA1 and LMO4 mRNA expression can help predict outcome to erlotinib

Safety and Efficacy of Axicabtagene Ciloleucel versus Standard of Care in Patients 65 Years of Age or Older with Relapsed/Refractory Large B-Cell Lymphoma

Purpose: Older patients with relapsed/refractory (R/R) large B-cell lymphoma (LBCL) may be considered ineligible for curative-intent therapy including high-dose chemotherapy with autologous stem-cell transplantation (HDT-ASCT). Here, we report outcomes of a preplanned subgroup analysis of patients >= 65 years in ZUMA-7. Patients and Methods: Patients with LBCL refractory to or relapsed = 65 years were random-ized to axi-cel and SOC, respectively. Median EFS was greater with axi-cel versus SOC (21.5 vs. 2.5 months; median follow-up: 24.3 months; HR, 0.276; descriptive P = 3 adverse events occurred in 94% of axi-cel and 82% of SOC patients. No grade 5 cytokine release syndrome or neurologic events occurred. In the quality-of-life analysis, the mean change in PRO scores from baseline at days 100 and 150 favored axi-cel for EORTC QLQ-C30 Global Health, Physical Functioning, and EQ-5D-5L visual analog scale (descriptive P = 65 and = 65 years with R/R LBCL

Antitumor activity of lurbinectedin in second-line small cell lung cancer patients who are candidates for re-challenge with the first-line treatment

Introduction: The National Comprehensive Cancer Network guidelines recommend re-challenge with the first-line treatment for relapsed small cell lung cancer (SCLC) with chemotherapy-free interval (CTFI)=180 days. A phase II study (NCT02454972) showed remarkable antitumor activity in SCLC patients treated with lurbinectedin 3.2 mg/m2 1 -h intravenous infusion every 3 weeks as second-line therapy. We report results for the pre-planned subset of patients with CTFI = 180 days. Material and Methods: Twenty patients aged =18 years with pathologically proven SCLC diagnosis, pretreated with only one prior platinum-containing line, no CNS metastases, and with CTFI = 180 days were evaluated. The primary efficacy endpoint was the overall response rate (ORR) assessed by the Investigators according to RECIST v1.1. Results: ORR was 60.0 % (95 %CI, 36.1-86.9), with a median duration of response of 5.5 months (95 %CI, 2.9-11.2) and disease control rate of 95.0 % (95 %CI, 75.1-99.9). Median progression-free survival was 4.6 months (95 %CI, 2.6-7.3). With a censoring of 55.0 %, the median overall survival was 16.2 months (95 %CI, 9.6-upper level not reached). Of note, 60.9 % and 27.1 % of patients were alive at 1 and 2 years, respectively. The most common grade 3/4 adverse events and laboratory abnormalities were hematological disorders (neutropenia, 55.0 %; anemia; 10.0 % thrombocytopenia, 10.0 %), fatigue (10.0 %) and increased liver function tests (GGT, 10 %; ALT and AP, 5.0 % each). No febrile neutropenia was reported. Conclusion: Lurbinectedin is an effective treatment for platinum-sensitive relapsed SCLC, especially in patients with CTFI = 180 days, with acceptable safety and tolerability. These encouraging results suggest that lurbinectedin can be another valuable therapeutic option rather than platinum re-challenge

La jungle de Calais : les migrants, la frontière et le camp

International audienceD’avril 2015 à octobre 2016, jusqu’à dix mille migrants ont vécu dans des conditions extrêmement précaires au sein de la «  Jungle  » de Calais, suscitant autant de passions, de polémiques et de peurs que de solidarités.Michel Agier, a réuni une équipe composée de chercheurs et d’acteurs de terrain (Yasmine Bouagga, Maël Galisson, Cyrille Hanappe, Mathilde Pette,et Philippe Wannesson) pour fournir les clés de compréhension de l’événement Calais – un objet politique, médiatique et symbolique inédit. Car toutes les indignations dont la Jungle a été l’objet, toutes les violences physiques et morales contre ses habitants et toutes les solidarités qui l’ont aidée à tenir cristallisent les questions qui traversent aujourd’hui le monde aux prises avec la mobilité  : comment se définit un «  nous  » local, national et européen face aux «  autres  » et à soi-même  ? Comment peut-on – ou non – réinventer l’hospitalité à partir des camps  ? Quel avenir s’imagine dans ces lieux de mise à l’écart et d’exception qui finissent par ressembler à des occupations et à de nouveaux espaces politiques  ? »

La jungle de Calais

International audienceD’avril 2015 à octobre 2016, jusqu’à dix mille migrants ont vécu dans des conditions extrêmement précaires au sein de la «  Jungle  » de Calais, suscitant autant de passions, de polémiques et de peurs que de solidarités.Michel Agier, a réuni une équipe composée de chercheurs et d’acteurs de terrain (Yasmine Bouagga, Maël Galisson, Cyrille Hanappe, Mathilde Pette,et Philippe Wannesson) pour fournir les clés de compréhension de l’événement Calais – un objet politique, médiatique et symbolique inédit. Car toutes les indignations dont la Jungle a été l’objet, toutes les violences physiques et morales contre ses habitants et toutes les solidarités qui l’ont aidée à tenir cristallisent les questions qui traversent aujourd’hui le monde aux prises avec la mobilité  : comment se définit un «  nous  » local, national et européen face aux «  autres  » et à soi-même  ? Comment peut-on – ou non – réinventer l’hospitalité à partir des camps  ? Quel avenir s’imagine dans ces lieux de mise à l’écart et d’exception qui finissent par ressembler à des occupations et à de nouveaux espaces politiques  ? »

Prognostic value of KRAS G12C in advanced non-small cell lung cancer with high PD-L1 expression treated with upfront immunotherapy: a systematic review and meta-analysis

AIM: This study aims to evaluate the prognostic role of the KRAS G12C mutation in patients with advanced non-small cell lung cancer and PD-L1 expression ≥50% who are treated with immune checkpoint inhibitor monotherapy. METHODS: We conducted a systematic review of clinical studies fulfilling the following criteria: (1) enrolling patients with advanced/metastatic non-small cell lung cancer with high PD-L1 tumour expression receiving first-line therapy with anti-PD-(L)1 immune checkpoint inhibitors; (2) comparing the outcomes of patients with the KRAS G12C mutation to those without this mutation, and (3) reporting overall survival and progression-free survival (PFS). The electronic databases Medline, EMBASE, Cochrane and Google Scholar, along with reference lists, were systematically searched. RESULTS: We identified four publications that fulfilled the inclusion criteria, comprising a total of 469 patients. Of these, two studies reported hazard ratios (HR) for PFS, resulting in a final pooled patient sample of 163 for the meta-analysis. In patients with non-small cell lung cancer who received anti-PD-(L)1 monotherapy, the presence of a KRAS G12C mutation was associated with improved PFS compared to patients with KRAS wild-type tumours, with a pooled hazard ratio of 0.39 and a 95% Confidence Interval (CI) of 0.25–0.63. Among all patients with KRAS mutations, those harbouring a KRAS G12C mutation had improved PFS compared to patients with any other KRAS mutation (pooled HR 0.33, 95% CI 0.19–0.57). CONCLUSIONS: Patients with non-small cell lung cancer who have the KRAS G12C mutation and high PD-L1 expression demonstrate favourable PFS with first-line PD-(L)1 immune checkpoint inhibitor monotherapy compared to patients with KRASwt or other KRAS mutations and high PD-L1 expression

Recent developments and advances in secondary prevention of lung cancer

Lung cancer prevention may include primary prevention strategies, such as corrections of working conditions and life style - primarily smoking cessation - as well as secondary prevention strategies, aiming at early detection that allows better survival rates and limited resections. This review summarizes recent developments and advances in secondary prevention, focusing on recent technological tools for an effective early diagnosis