This study aimed to compare the differences in characteristics and prognoses between Asian and white patients receiving immunotherapy for nonsmall cell lung cancer (NSCLC). We studied 390 patients who received atezolizumab as part of the POPLAR or OAK trial, and analyzed the differences in baseline characteristics, outcomes and genetic mutations in blood samples between Asian and white patients. Overall survival (OS) was longer in Asian compared to white patients (median OS: 18.7 vs. 11.1 months; p = 0.005). Race was identified as an independent prognostic factor for OS (Asian vs. white: hazard ratio 0.647, 95% confidence interval 0.447–0.936, p = 0.021), together with performance status, histology, baseline sum of the longest tumor diameters (BLSLD) and number of metastatic sites. The two groups also differed in terms of characteristics including smoking history, BLSLD, epidermal growth factor receptor (EGFR) mutation frequency, programmed death‐ligand 1 expression and blood‐based tumor‐mutation burden. Blood mutations of STK11, EGFR, KEAP1, POLE, GRM3, ATM and STAG2 were associated with treatment response, and TP53, KEAP1, APC, RB1, CREBBP, EPHA5 and STAG2 mutations were associated with OS. The blood‐based mutation profiles differentiated between Asian and white patients, especially in relation to EGFR (23.8 vs. 8.5%), TP53 (30.2 vs. 46.9%) and STK11 (1.6 vs. 12.3%) mutations (all p < 0.05). The different clinicopathological features and mutation profiles in Asian and white patients may explain the superior outcome following atezolizumab treatment in Asian patients with NSCLC. The results of this study have important implications for further studies on racial disparities in relation to immunotherapy.

A significant association between high blood-based tumor mutational burden (bTMB) and improved progression-free survival (PFS) was observed in advanced non-small cell lung cancer (NSCLC) receiving atezolizumab. However, this result was unrepeatable in a recent prospective study. We hypothesized that there might be a non-linear association between bTMB and survival. This study used the clinical and genetic data from POPLAR (n = 105, training set) and OAK (n = 324, validation set) trials. The non-linear association between bTMB and survival was assessed using restricted cubic spline (RCS). The cutoff values for bTMB were calculated via X-tile software. Non-linear relationships were observed between bTMB and PFS and overall survival (OS) in RCS plots (both P non-linearity < 0.001). The optimal cutoff values of bTMB for predicting PFS and OS were 7 and 14 mutations/Mb, respectively. The median PFS and OS of patients with low and high bTMB were significantly longer than those of patients with medium bTMB in the training, validation, and combined sets. Low and high bTMB were also associated with longer PFS and OS in high-programmed death-ligand 1 (PD-L1) expression population. In conclusion, there was a positive non-linear association between bTMB and survival in NSCLC patients receiving atezolizumab. Patients with low bTMB could also derive benefit from immunotherapy.

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BackgroundAnlotinib has been demonstrated its anti-tumor efficacy on non-small cell lung cancer (NSCLC) in clinical trials at 3rd line. However, anlotinib resistance occurs during its administration, and the underlying mechanism is still unclear.MethodsAnlotinib resistant lung cancer cell line NCI-H1975 was established in vitro. Toxicologic effects undergoing anlotinib stress were observed upon NCI-H1975 cells and anlotinib resistant NCI-H1975 cells, respectively. Transcriptome profiling was performed to screen anlotinib resistance-associated genes between NCI-H1975 cells and anlotinib resistant NCI-H1975 cells. Functional assays were performed to examine the correlations between CXCL2 gene expression and anlotinib resistance.ResultsWe found anlotinib inhibits cell proliferation and cell viability in NCI-1975 cells, whereas it attenuates these activities in anlotinib resistant NCI-H1975 cells. Transcriptome profiling analysis identified 769 anlotinib-responsive genes enriched in the biological processes of microtubule-based process, cytoskeleton organization, and wound healing. Furthermore, we found 127 genes are associated with anlotinib resistance. In particular, we demonstrated that CXCL2 contributes to anlotinib resistance in NCI-H1975 cells.ConclusionsThis study suggested that CXCL2 is involved in anlotinib resistance in NCI-H1975 cells and provided an insight for understanding the resistant mechanism of anlotinib.Electronic supplementary materialThe online version of this article (10.1186/s12920-019-0482-y) contains supplementary material, which is available to authorized users.