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360 Background: Angiogenesis plays an important role in NET development and progression. Axitinib is a potent and selective VEGFR-1,2,3 inhibitor, with proven activity against several vascular-dependent solid tumors. The aim of this randomized, double-blind phase II/III study was to assess the efficacy of axitinib in patients with advanced G1-2 extra-pancreatic NETs. Methods: Eligible pts were randomized (1:1) to receive octreotide LAR (30 mg IM q4w) with axitinib (5 mg BID) or placebo BID until disease progression or unacceptable toxicity. Pteswere stratified by time from diagnosis to study entry ( > or < 12m), primary tumor site (GI tract vs non-GI) and Ki-67 index (< 5% vs > 5%). Prior therapy with SSA, IFN and up to 2 lines of systemic treatment was allowed, but not prior VEGF- or VEGFR-targeted drugs. Clinical and/or radiological disease progression within 12 months prior to study entry was required. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), time to progression, overall response rate (ORR), duration of response, biochemical response and safety. Results: 256 pts were randomized (106 in the Phase II part, and 150 additional pts in the Phase III part), 126 to axitinib and 130 to placebo. The main characteristics of the study population were: median age 61 years (range: 21-85), 52% male, PS 0-1 (64-35%), G1-2 (29%-71%), primary tumor site GI (40%)-Lung (17%)-Other (32%). Prior therapies included: SSA (46%), everolimus (13%), chemotherapy (13%), TACE (5%) and PRRT (2%). ORR was significantly higher in axitinib- vs placebo-treated patients (17.5% vs 3.8%, p = 0.0004). PFS per investigator assessment also favored axitinib vs placebo-treated patients, although the difference did not reach statistical significance (median PFS 17.2 vs 12.3 months, respectively, HR 0.816, p = 0.169). Grade 3-4 treatment-related AEs occurred more frequently in the axitinib vs placebo arm (52% vs 13.8%), and included hypertension (21% vs 6 %), cardiac disorders (3.2% vs 0.7%), diarrhoea (13% vs 1.5 %), asthenia (9% vs 3%) and nausea&vomiting (2% vs 0.7%). There were 3 treatment-related deaths, 1 in the axitinib arm (cardiac failure) and 2 in the placebo arm (myocardial infarction and hepatorenal syndrome). Conclusions: Although the study failed to demonstrate a significant PFS benefit per investigator assessment, axitinib in combination with octreotide LAR demonstrated activity and had a tolerable safety profile in patients with advanced G1-2 extra-pancreatic NETs. Data base cleaning and central blinded radiological PFS assessment are currently ongoing. Clinical trial information: NCT01744249.

e14247 Background: The neutrophil-lymphocyte (N / L) ratio is a marker of general immune response in different stress situations, having shown a relationship between the quotient and the evolution of patients treated with immunotherapy (IT), emphasizing the importance of inflammation in these patients. Methods: In order to evaluate this relationship in a context of usual clinical practice, we performed a retrospective review of patients with pulmonary neoplasia who received IT treatment in the first line or successive, between November 2015 and December 2018, excluding those who received treatment within of clinical trial. Data were collected from the clinical history of each patient, with special attention to baseline neutrophil and lymphocyte numbers, objective response to therapy by criteria iRECIST 1.1 after 3 months of treatment and overall survival (OS) defined from the beginning of treatment until death by progression of the disease. Results: 92 patients (29 women and 63 men) with a median age of 64 years (44-79) were analyzed. 15 (16,3%) patients (p) received immunotherapy as first line treatment, 65.2% (60 p) received it as 2nd line and 18,5% (17 p) as 3rd or succesive lines. The average number of cycles received was 14 (1-52). Regarding the type of IT, 54 p (58,7%) received treatment with Nivolumab, 33 patients (36%) with Pembrolizumab and 5 patients (5.3%) were treated with Atezolizumab. Two stretches of baseline N / L ratios ≤5 (low) and > 5 (high) were defined. Low ratio N / L (≤5) was identified in 62p (67.4%) of the patients treated with IT and high ratio N/L ( > 5) in 30p (32,6%). Of the 62 patients with a low ratio: 41p (66.1%) had some type of response or stabilization of their disease, 13 patients (21%) had progression and 8 patients (12.9%) received less than three months of treatment, 6 patients for PS deterioration and the other 2 patients continue with the treatment and are pending reevaluation. Among the 30 patients with high N / L quotient: 7p (23.3%) presented response or stabilization of the disease, 23 patients (76,7%) presented progression or treatment was interrupted due to deterioration of the ECOG. The average survival in the group with a low N / L ratio (≤5) was 213 weeks compared to the group with a high N / L ratio ( > 5) 144 weeks (p < 0.05). Conclusions: The N / L ratio has been identified in some studies as an adverse prognostic factor in patients treated with IT. Our data from the usual clinical practice support this theory. If these findings are confirmed in future studies, it could be used as a response biomarker for better patient selection.