Vemurafenib in non-small-cell lung cancer patients with BRAFV600 and BRAFnonV600 mutations.

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 AcSé 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.

Multicentre phase II study of cisplatin-etoposide chemotherapy for advanced large-cell neuroendocrine lung carcinoma: the GFPC 0302 study.

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).

Real world data of efficacy and safety of erlotinib as first-line TKI treatment in EGFR mutation-positive advanced non-small cell lung cancer: Results from the EGFR-2013-CPHG study.

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<0.001) but not with brain metastasis (HR=1.67, P=0.278). 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.

[Aneurysm of a saphenous vein bypass graft to coronary artery: a case report discovered as an incidental finding]. / Anévrisme d'un pontage veineux aortocoronarien: a propos d'un cas de découverte fortuite.

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.

[Study KBP-2010-CPHG: inclusion of new cases of primary lung cancer diagnosed in general hospital pneumology departments between 1st January and 31 December 2010]. / Étude KBP-2010-CPHG: recueil des nouveaux cas de cancer bronchopulmonaire primitif diagnostiqués dans les services de pneumologie des centres hospitaliers généraux du 1(er) janvier au 31 décembre 2010.

INTRODUCTION: The College of General Hospital Respiratory Physicians (CPHG) is following up the KBP-2000-CPHG study, performed ten years ago, with a new observational epidemiological study of primary lung cancer. PATIENTS AND METHODS: The study includes all new cases of primary lung cancer diagnosed on histology or cytology between 1 January and 31 December 2010 and managed by one of the general hospital pneumology departments participating in the study. The primary objective is to estimate five-year mortality and to analyze risk factors. Secondary objectives are to describe the characteristics of this patient population and their management, and to estimate one, four and five-year survival rates. These data will be compared to those of the KBP-2000-CPHG study. The four-year prognosis score developed in 2000 will also be assessed in the new study. Data are collected by standardized questionnaire with exhaustiveness control. EXPECTED RESULTS: One hundred and eight investigating centers have agreed to participate; 4000 to 5000 new cases of primary lung cancer should be collected and analyzed. CONCLUSION: The study will describe the characteristics of patients presenting with primary lung cancer in the participating pneumology departments during the year 2010, and their diagnostic and therapeutic management, and assess changes over the last ten years.