The treatment landscape for patients with advanced non-small cell lung cancer, who do not harbour an oncogenic driver abnormality, has changed dramatically over the last years. Second-generation antiangiogenic agents, such as nintedanib and ramucirumab, and particularly PD-1/PD-L1 inhibitors, such as nivolumab, pembrolizumab and atezolizumab have shown to prolong survival in pretreated non-small cell lung cancer patients. Immune checkpoint inhibition in the treatment of advanced non-small cell lung cancer comes with the promise of durable responses in responding patients. Nevertheless, one must appreciate that the average response rate seen with these PD-1/PD-L1 targeting agents is only about 20%. While PD-L1 testing may be used as an enrichment biomarker, a substantial proportion of patients still do not benefit from these agents. They could benefit from alternative therapeutic options, including novel anti-angiogenic agents. In this paper, a treatment algorithm is proposed that aims to optimise the second-line treatment choice for patients with lung adenocarcinoma, based on the available clinical data.