Predictive factors for combined anti-PD-1 and anti-angiogenic therapy in multiline treatment of advanced non-small cell lung cancer.

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e15059 Background: Immune checkpoint inhibitors (ICIs), such as PD-1/ PD-L1 inhibitors, have made a significant breakthrough in lung cancer first-line treatment. However, there are few reports on stratification, therapeutic response and prognosis prediction of NSCLC patients treated with immunotherapy combined with anti-angiogenic therapy in multiline therapy. The aim of this study was to investigate the clinical efficacy of anti-PD-1 plus anti-angiogenic therapy in the second-line or multiline treatment of NSCLC, and to explore potential predictive biomarkers for response and prognosis in this combined therapy. Methods: A total of 22 advanced NSCLC patients were recruited in this study, in which 14 patients received this combined immunotherapy as second-line therapy, and 8 patients as multiline therapy. Genomic profiles were determined with blood by a 451-gene next-generation sequencing panel. Sequencing data were analyzed with R packages and statistics analysis was performed with SPSS 20 software. P ≤ 0.05 was regarded as statistically significant. Results: All patients were followed up until progression or the end of this study. The objective response rate (ORR) assessed by an independent radiology review was 22.7%, and the median progression-free survival (PFS) time for all patients was 5.25 months. Surprisingly, the pre-therapeutic blood tumor mutation burden (bTMB) could not discriminate clinical benefit from non-benefit group in this combined therapy (P = 0.167). However, we found that the concentration of pre-therapeutic blood circulating free DNA (cfDNA) was an independent predictor of PFS (HR = 27.75, P = 0.003), in which higher cfDNA concentration correlated with poorer outcomes. Meanwhile, patients harboring MIKI67 gene mutations or gene variations related to hyper-progressive disease showed significantly shorter PFS time (p < 0.05). In addition, patients with negative ctDNA before therapy might benefit more from this combined immunotherapy (P = 0.068). Conclusions: Our study suggested that the combined strategies may improve clinical efficacy of ICIs in second and multiline therapy. The pre-therapeutic bTMB was not predictive for clinical benefit in multiline combined therapy. Patients with pre-therapeutic high concentration of cfDNA, MIKI67 mutations or gene variations related to hyper-progressive disease may be less likely to benefit from the combined therapy. Our findings may improve the prediction of therapeutic effect and prognosis in future combined treatment involving immunotherapy.