OBJECTIVES: The relative efficacy of nintedanib + docetaxel versus other second-line agents approved in patients with adenocarcinoma histology NSCLC was evaluated using network meta-analysis (NMA) in 2015. Here we provide an update including new therapeutic options. METHODS: A systematic literature review found 3 new trials which fit to the previously published inclusion criteria or present subgroup results for the population of interest. The NMA of progression-free survival (PFS) and overall survival (OS) was updated following the previously published methods. RESULTS: Nintedanib + docetaxel was superior vs. docetaxel, erlotinib and gefitinib (Nintedanib + docetaxel vs. docetaxel: OS HR=0.83 (95% CI: 0.70–0.99), PFS HR=0.77 (0.6–0.96); vs. pemetrexed: OS HR=0.82 (0.60–1.11), PFS HR=0.84 (0.61–1.15); vs. erlotinib: OS HR=0.64 (0.46–0.90), PFS HR=0.70 (0.50–0.99); vs. gefitinib: OS HR=0.59 (0.36–0.96), PFS HR=0.45 (0.28–0.72)). Results comparing nintedanib vs. ramucirumab and nivolumab confirmed overall similarity. However, hazard ratios vs. nivolumab pointed into a direction in favour of nivolumab for OS (HR=1.20 (0.92–1.58)) but in favour of nintedanib for PFS (HR=0.91 (0.68–1.21)). Because significant interaction p-values indicate that PD-L1 expression is a relevant effect modifier for nivolumab, an exploratory subgroup analysis was conducted. Results indicated superiority of nivolumab in subgroups with high PD-L1 expression level, whereas the results were consistently pointing into a favourable direction for nintedanib in all subgroups with low (<1%, <5%, <10%) PD-L1 expression level, in particular with regard to PFS (e.g. <10% PD-L1 expression: PFS HR=0.62 (0.44–0.87); OS HR=0.83 (0.60–1.15)). CONCLUSIONS: Results demonstrated superiority of nintedanib + docetaxel vs. several established therapies and similar efficacy compared to the new therapeutic options ramucirumab and nivolumab with potential differences in subgroups according to PD-L1 expression level. Results confirm nintedanib’s place in NSCLC therapy, especially for patients not suitable for PD1 treatment or with a low PD-L1 expression level.