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Background BRAF mutations occurring in 1%–5% of patients with non-small-cell lung cancer (NSCLC) are therapeutic targets for these cancers but the impact of the exact mutation on clinical activity is unclear. The French National Cancer Institute (INCA) launched the AcSe vemurafenib trial to assess the efficacy and safety of vemurafenib in cancers with various BRAF mutations. We herein report the results of the NSCLC cohort. Patients and methods Tumour samples were screened for BRAF mutations in INCA-certified molecular genetic centres. Patients with BRAF-mutated tumours progressing after ≥1 line of treatment were proposed vemurafenib 960 mg twice daily. Between October 2014 and July 2018, 118 patients were enrolled in the NSCLC cohort. The primary outcome was the objective response rate (ORR) assessed every 8 weeks (RECIST v1.1). A sequential Bayesian approach was planned with an inefficacy bound of 10% for ORR. If no early stopping occurred, the treatment was of interest if the estimated ORR was ≥30% with a 90% probability. Secondary outcomes were tolerance, response duration, progression-free survival (PFS), and overall survival (OS). Results Of the 118 patients enrolled, 101 presented with a BRAFV600 mutation and 17 with BRAFnonV600 mutations; the median follow-up was 23.9 months. In the BRAFnonV600 cohort, no objective response was observed and this cohort was stopped. In the BRAFV600 cohort, 43/96 patients had objective responses. The mean Bayesian estimated success rate was 44.9% [95% confidence intervals (CI) 35.2%–54.8%]. The ORR had a 99.9% probability of being ≥30%. Median response duration was 6.4 months, median PFS was 5.2 months (95% CI 3.8–6.8), and OS was 10 months (95% CI 6.8–15.7). The vemurafenib safety profile was consistent with previous publications. Conclusion Routine biomarker screening of NSCLC should include BRAFV600 mutations. Vemurafenib monotherapy is effective for treating patients with BRAFV600-mutated NSCLC but not those with BRAFnonV600 mutations. Trial registration ClinicalTrials.gov identifier: NCT02304809.

Background Phase III clinical trials have demonstrated the merits of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKI) in the treatment of non-small cell lung cancer (NSCLC) patients with EGFR-activating mutations. Using a cohort of unselected patients treated with erlotinib, we sought to further describe patient and tumour characteristics, and to evaluate their progression-free survival (PFS) and overall survival (OS). Methods Overall, 44 pulmonologists included patients with the required characteristics as follows: Stage IIIB-IV NSCLC, EGFR-activating mutation, age ≥ 18 years, and having to start erlotinib therapy or receiving erlotinib therapy as the first-line TKI, regardless of treatment-line. The analyses were performed using R software, with survival rates calculated according to the Kaplan–Meier method. Results A total of 177 patients, aged 72 years on average, were enrolled over a 2-year period. The cohort included 123 women (69.5%), 158 Caucasians (89.3%), 112 non-smokers (63.2%), and 167 adenocarcinomas (94.3%), at either stage IIIB (21) or IV (156), with a good performance status (PS 0–1, 127). Overall, 40 exhibited brain metastases at baseline (22.6%), while 75 had undergone earlier treatment (42.4%). Median PFS was 11.7 months and OS 25.8 months, with respectively a 1-year rate of 48.6% and 74%. The risk of death correlated with ECOG status (PS = 2, HR = 4.48, P Conclusions This study has confirmed erlotinib's efficacy and safety for unselected patients, with PFS and OS comparable to those obtained in phase III trials.

Resume Le vieillissement pulmonaire est un phenomene naturel caracterise par une deterioration progressive des fonctions de reparation des structures pulmonaires. Celui-ci resulte de plusieurs mecanismes parmi eux l’immunosenescence, l’accroissement du stress oxydatif et l’apoptose defaillante. L’immunosenescence est responsable d’un accroissement de la morbidite et de la mortalite respiratoire dans de multiples domaines : infections bacteriennes et virales, asthme, BPCO. L’immunosenescence ne s’exprime pas de facon homogene, d’une affection a l’autre : l’immunite adaptative est, en general, deprimee et l’immunite innee parfois tres augmentee. Ce deflcit de l’immunite est renforce, au fil des ans, par la denutrition et certaines comorbidites L’immunosenescence doit nous conduire a repenser notre approche therapeutique du patient âge : « nouveaux » vaccins, « cytokine therapy », supplementation en anti-oxydants…

Resume Introduction Le College des pneumologues des hopitaux generaux (CPHG) propose de mener, dix ans apres l’etude KBP-2000-CPHG, une nouvelle etude epidemiologique observationnelle sur le cancer bronchopulmonaire (CBP) primitif. Patients et methodes Cette etude prospective porte sur tous les nouveaux cas de CBP primitif diagnostiques histologiquement ou cytologiquement entre le 1 er janvier et le 31 decembre 2010, et suivis dans un service de pneumologie d’un des centres hospitaliers generaux (CHG) participants. Son objectif principal est d’estimer la mortalite a cinq ans de ces patients et d’en rechercher les facteurs de risque. Ses objectifs secondaires sont de decrire les caracteristiques de cette population de patients, les modalites de leur prise en charge et d’estimer les taux de survie a un, quatre et cinq ans. Ces donnees seront ensuite comparees a celles obtenues lors de l’etude KBP-2000-CPHG. Le score pronostique a quatre ans developpe lors de l’etude KBP-2000-CPHG sera egalement teste dans cette etude. Les donnees sont recueillies au moyen d’un questionnaire standardise avec controle de l’exhaustivite. Resultats attendus Cent huit centres investigateurs ont accepte de participer a l’etude. Quatre mille a 5000 nouveaux cas de CBP primitif devraient etre collectes et analyses. Conclusion Cette etude permettra de decrire les caracteristiques des patients presentant en 2010 un CBP primitif suivis dans les CHG participant a l’etude, ainsi que leur prise en charge diagnostique et therapeutique. Elle va egalement permettre d’evaluer les changements survenus en dix ans.

We report a case of aortocoronary bypass graft aneurysm revealed by exertional dyspnea and presenting as an anterior mediastinal mass at the unenhanced computed tomography scan. The diagnosis has been established using combined contrast-enhanced CT scan which specified the vascular nature of the mass and coronary angiography which connected it to the aorto-marginal branch saphenous vein graft. This case illustrates the frequently asymptomatic expression of aneurysm and the importance of combined imaging modalities for the diagnosis.

Background The optimal treatment of large-cell neuroendocrine carcinoma (LCNEC) of the lung remains unclear. Here, our primary objective was to assess the efficacy of cisplatin–etoposide doublet chemotherapy in advanced LCNEC. Accuracy of the pathological diagnosis and treatment toxicity were assessed as secondary objectives. Patients and methods Prospective, multicentre, single-arm, phase II study with a centralised review of treatment-response and pathological data. Patients had untreated performance status (PS) 0/1 stage IV/IIIB LCNEC and received cisplatin (80 mg/m22 d1) and etoposide (100 mg/m22 d1-3) every 21 days. Results Eighteen centres included 42 patients (mean age, 59 ± 9 years; 69% men; median of four cycles/patient). At least one grade-3/4 toxicity occurred in 59% of patients (neutropaenia, thrombocytopaenia, and anaemia in 32%, 17%, and 12%, respectively). The median progression-free survival (PFS) and overall survival (OS) were 5.2 months (95% confidence interval, CI, 3.1–6.6) and 7.7 months (95% CI, 6.0–9.6), respectively. The centralised pathologist review reclassified 11 of 40 (27.5%) patients: 9 as small-cell lung cancer, 1 as undifferentiated non-small-cell lung cancer, and 1 as atypical carcinoid. Survival data were not significantly changed by excluding the reclassified patients. Conclusions The pathological diagnosis of LCNEC is difficult. The outcomes of advanced LCNEC treated with cisplatin–etoposide doublets are poor, similar to those of patients with advanced small-cell lung carcinoma (SCLC).

Aim: The use of a CGA is recommended to detect a patient's vulnerability but its integration in treatment decision making has never been prospectively evaluated. Our main objective was to test if the use of CGA in the allocation of treatment could improve the management of advanced NSCLC in first line. Methods: Randomized, multicentric, prospective phase III study in patients ≥70 y, PS 0-2 with stage IV NSCLC. Arm A standard algorithm of chemotherapy allocation: carboplatin based doublet in PS ≤ 1 and age ≤75y, docetaxel in PS =2 or age >75y. Arm B treatment allocation based on CGA: carboplatin based doublet for fit patients, mono-therapy for vulnerable patients and BSC for frail patients. Four cycles were given every three weeks. Main endpoint: time to failure free survival (TFFS) Secondary endpoints: overall Response Rate (ORR), overall survival (OS), toxicity, QoL and life expectancy adjusted on QoL. QoL was assessed during treatment by EQ-5D health questionnaire at baseline, weeks 6, 12, 20, 28, and 36. A mixed-effects model was used, to compare the utility score and therefore the QOL between arms A and B. Results: 493 patients were randomized from 01/2010 to 01/2013 by 45 centers. Respectively in arms A and B, 34.4% and 47% of patients received a carboplatin-based doublet, 65.6% and 31.4% received docetaxel and in arm B 21.5% received BSC. Median TFFS was 3.2 m, 95%CI:[2.9; 4.1] for standard arm and 3.1 m, 95%CI:[2.7; 4.4] for experimental arm, p = 0.71. Compliance with QoL was 87% at baseline and respectively 66%, 65%, 54%, 60% and 57% at week 6, 12, 20, 28 and 36. The utility score at each evaluation is superior in the experimental arm than in the standard arm, but this difference is significant only at week 36 (p = 0.02). Using a linear mixed generalized model, the utility score tends to decrease over time and is not significantly different between the two arms (p = 0.85). Life expectancy adjusted on QoL was 130.1 days in standard arm and 133.3 days in experimental arm, p = 0.51. Conclusions: ESOGIA did not show a superiority of a CGA-based treatment allocation. In the experimental arm, more patients received a carboplatin-based doublet and 21% of frail patients received an exclusive BSC management. Despite a trend in favor of CGA arm, there is no significant difference in terms of QoL score and life expectancy adjusted on QoL. Further sudies are needed for GA in NSCLC elderly patients. Disclosure: C. Chouaid: advisory board LILLY; H. Lena: advisory board Lilly. All other authors have declared no conflicts of interest.

e18018 Background: A few prospective studies concerning diagnosis and treatment of large cell neuroendocrine lung cancer have been published. After the new World Health Organization classification of lung tumours in 1999, results of previous or retrospective studies based on the old classification seemed unexplainable. So the GFPC started a prospective study, to establish the efficiency of cisplatinum/etoposide chemotherapy for patients with LCNE lung cancer, diagnosed on the basis of the Travis's criteria. 50 patients were planned. Methods: Patients with stage IV and stage III B (with neoplasic pleural effusion) were selected; treatment was three cycles of cisplatinum 80 mg/m2 d1/etoposide 100 mg/m2 d1d2d3 and two more cycles in case of objective response or stable disease. The primary objective is the efficiency, in term of objective response and survival rate, the secondary objectives, the improvement of the pathologic diagnosis, with validation of the paranuclear granular expression of a large spectru...