Although not statistically significant, clinically important differences in the median, 2-, 3-, and 4-year survival rates were observed, with a trend in favor of concurrent chemoradiation therapy, suggesting that is the optimal strategy for patients with locally advanced NSCLC.

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17. Herder GJ, van Tinterent TH, Golding RP et al. Clinical prediction 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 treatmentresponse 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). Key words: carcinoma, clinical trial phase II, large cell neuroendocrine tumours, small-cell lung cancer introduction Large-cell neuroendocrine carcinoma (LCNEC) of the lung accounts for no more than 1% of all lung cancers. The typical histological features, first described in 1991 [1, 2], include large cells with abundant cytoplasm, a high mitotic rate, extensive necrosis, and a neuroendocrine growth pattern. The World Health Organisation currently classifies LCNEC as a distinct subtype of pulmonary large-cell carcinoma [3] and, therefore, as a subtype of non-small-cell lung carcinoma (NSCLC). However, LCNEC lacks the specific histologic features of NSCLC such as glandular or squamous differentiation, but instead displays evidence of neuroendocrine differentiation reminiscent of small-cell lung carcinoma (SCLC), although the malignant cells in SCLC are smaller, with scant cytoplasm, and invade the tissues in sheets. LCNECLCNEC shares genetic alterations with SCLC [4]. The higher mitotic rates and more extensive necrosis seen in LCNEC and SCLC are in contrast to the lower-grade neuroendocrine tumours, i.e. typical and atypical carcinoids. LCNEC and SCLC also share clinical characteristics including a preponderance of males and smokers and an aggressive clinical course [5][6][7][8][9]. The clinical outcome of LCNEC patients is poor, with overall 5-year survival rates ranging from 15% to 57%. Studies have demonstrated signifi...

Background: BRAF mutations occurring in 1%e5% 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 BRAF V600 mutation and 17 with BRAF nonV600 mutations; the median follow-up was 23.9 months. In the BRAF nonV600 cohort, no objective response was observed and this cohort was stopped. In the BRAF V600 cohort, 43/96 patients had objective responses. The mean Bayesian estimated success rate was 44.9% [95% confidence intervals (CI) 35.2%e54.8%]. 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 3.8e6.8), and OS was 10 months (95% CI 6.8e15.7). The vemurafenib safety profile was consistent with previous publications. Conclusion:Routine biomarker screening of NSCLC should include BRAF V600 mutations. Vemurafenib monotherapy is effective for treating patients with BRAF V600 -mutated NSCLC but not those with BRAF nonV600 mutations. Trial registration: ClinicalTrials.gov identifier: NCT02304809.