P2.01-022 Nintedanib/Docetaxel Efficacy in Advanced Lung Adenocarcinoma Treated with 1L Chemotherapy/2L Immunotherapy in Nintedanib NPU

Both antiangiogenic agents (nintedanib and ramucirumab) in combination with docetaxel and monotherapy with anti-PD-1/ PD-L1 immunotherapy have demonstrated efficacy as second-line (2L) treatment of patients with stage IV lung adenocarcinoma. However, selection of optimal candidates and the most appropriate therapeutic sequence is under discussion. Herein, we report on the efficacy of the nintedanib/docetaxel combination following first-line (1L) platinum-based chemotherapy and subsequent immunotherapy in a real-world setting. From May 2014 to December 2015, 390 patients in 108 Spanish centers enrolled in the nintedanib Named Patient Use (NPU) program. NPU inclusion criteria were advanced lung adenocarcinoma with progressive disease following at least one line of platinum-based doublet chemotherapy. We retrospectively assessed patients that received immunotherapy (available through clinical trials or the nivolumab NPU program) prior to nintedanib/docetaxel. The aim of this analysis was to evaluate the efficacy of the nintedanib/docetaxel combination in this new clinical setting. Eleven patients met the inclusion criteria for this analysis: 64% were men; median age of 67 years (range, 44–74); ECOG performance status 0-1 in 100% of patients; median number of treatment lines before inclusion in the nintedanib NPU program was 2 (range, 2-3); PD-L1 expression was positive (unknown cut-off) in 6 patients and was not determined in 5 patients. Median progression-free survival (PFS) of first-line platinum-based chemotherapy was 3.3 months (range 1.4-9.4): 9 patients (82%) had progressed <6 months since start of first-line treatment and 4 patients (36%) had progressed <3 months. Second-line immunotherapy was pembrolizumab (36.5%), atezolizumab (36.5%) and nivolumab (27%). Median PFS of second-line immunotherapy was 2.3 months (range, 0.7-11). The overall response rate (ORR) to second-line immunotherapy was 18% with a disease-control rate (DCR) of 45%. The median number of treatment cycles of nintedanib/docetaxel was 4.5 (range, 2-22). Median PFS of nintedanib/docetaxel post first-line chemotherapy and second-line immunotherapy was 3.2 months (range, 1.4-14.6). Best response was partial response in 4 patients (36%), stable disease in 5 patients (46%), and progressive disease in 2 patients (18%), for an ORR of 36% and a DCR of 82%. Our experience in the Spanish nintedanib NPU program in patients with adenocarcinoma NSCLC pretreated with platinum-based doublet chemotherapy and immunotherapy suggests an encouraging ORR and DCR of nintedanib/docetaxel as compared with clinical trial results. These results reinforce the importance of an optimal therapeutic sequence for managing advanced lung adenocarcinoma: 1) Nintedanib/docetaxel should be the recommended second-line treatment in early progressors and 2) Possible chemosensitization effect by immunotherapy.