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Background CT-RT is the standard treatment for unresectable LA-NSCLC. P plus vinorelbine is widely used. Metronomic CT is a frequent administration of low doses of CT. mOV has shown good efficacy and improved safety, and could improve the RT effect. Our goal is to evaluate the efficacy and safety of P-mOV with radical RT in patients (pts) with LA-NSCLC. Methods Pts aged 18-75 years with histologically proven untreated and unresectable LA-NSCLC, adequate bone marrow, hepatic & renal function, ECOG PS0-1, received P 80mg/m2 D1 every 3 weeks combined with mOV 50mg/day on days D1, 3 & 5/weekly, 2 cycles (cy) as induction; patients without progression received 2 more cy of P at the same dose with mOV 30mg/day on D1, 3 & 5/weekly, concurrently with RT (66Gy in 6.5weeks). Primary endpoint was progression-free survival (PFS) by RECIST v1.1; secondary endpoints were: overall response rate (ORR), disease control rate (DCR), overall survival and safety profile. To guarantee an overall type-1 α error no greater than 0.05 and a type II (β) error 0.1 for PFS, a sample size of 67 pts was planned. Results Sixty-seven pts were recruited in 17 Spanish sites from 04/2016 to 06/2017. One of them didn’t meet all the inclusion criteria. We analyzed 66 pts included. Pt characteristics: Male 77.3%; median age 62 (range 33-75); PS 0/1 52/49%; smokers 53%; adenocarcinoma/squamous 43.9/42.4%; stage IIIA/B 42.4/57.6%. Only 32.3% of pts presented any grade 3-4 adverse event, including: neutropenia 20.0%; anemia 4.6%; febrile neutropenia 6.2%; esophagitis 3.1%; pneumonitis 1.5%. There were two deaths non-related to the treatment, during this period. Fifty-one pts have completed the treatment. ORR: 67.7%. DCR: 84.6%. With a median follow-up of 22.3 months (range 1.1-34.9), the median PFS is 11.5 months (CI95%; 9.9-15,4). Conclusions mOV-P with RT is as effective as the standard administration of vinorelbine, improving its safety profile. Clinical trial identification EudraCT 2015-003312-21. Legal entity responsible for the study Spanish Lung Cancer Group. Funding Pierre Fabre. Disclosure All authors have declared no conflicts of interest.

Background Post-operative platinum-based chemotherapy is the standard of care for resected NSCLC with nodal involvement. Expression of genes involved in DNA repair may have a prognostic role for the outcome. BRCA1 plays an important role in DNA repair pathways and could have a prognostic impact in this setting. The SCAT trial results found that for low BRCA1 levels subgroup Cis-Gem was superior to Cis-Doc and in high BRCA1 subgroup docetaxel single agent without platinum achieved similar survival to Cis-Doc. Risk of recurrence analysis according BRCA-1 levels has been performed. Methods From Jun/2007 to May/2013 591 patients were screened and 500 were included, 108 in the control arm treated with Cis-Docetaxel and 392 in the experimental arms treated with Cis-Gem, Cis-Doc or docetaxel alone according to terciles of BRCA1 expression level. With a cut-off September 30th 2018 and a median follow-up of 60 months, recurrence patterns were analysed for the whole group according BRCA1 levels in tumor tissue and comparison were made for risk of recurrence, single/multiple recurrence, thoracic/extrathoracic and metastatic sites (liver, bone, brain). Results Cumulative recurrence was evaluable in 232/456 patients (50.8%), 182/354 patients treated in the experimental arm and in 50/102 patients treated in the control arm (RR 1.04; 0.83-1.30) (p = 0.672). The majority of recurrences 159/232 (68.5%) were single site intrathoracic recurrences in 121/232 (52%) while 111/232 were extrathoracic (47.8%). Overall recurrence was 56.5% (113/200 p) for low tercile BRCA1 vs 48.8% (63/129) for intermediate tercile vs 44% (56/127) for high tercile (p = 0.025). No differences were seen between tercile groups for single site (p = 0.35), multiple site (p = 0.26), intrathoracic (p = 0.36), or extrathoracic (p = 0.38). More frequent distant metastatic sites were: bone (42 patients), brain (38 patients) and liver (11 patients). RIsk reduction was seen for brain metastases in patients with higher tercile BRCA1 (p = 0.003). Conclusions For NSCLC resected patients with lymph node involvement risk of recurrence remains high with a cumulative rate > 50%. Relative risk of recurrence was lower for tumors with higher BRCA1 levels. Distant metastases were seen in 47.8% of patients. Brain metastases risk was significant lower for patients with low BRCA1 expression. BRCA1 levels acts as a prognostic factor in early stages NSCLC. Clinical trial identification EudraCT: 2007-000067-15; NCT 00478699. Legal entity responsible for the study Spanish Lung Cancer Group - Grupo Espanol Cancer de Pulmon. Funding Sanofi Aventis. Disclosure All authors have declared no conflicts of interest.