Recently, immune checkpoint inhibitors have shown survival advantage over chemotherapy in the treatment of advanced non-small cell lung cancer (NSCLC). This meta-analysis was conducted to gather and analyze the available evidence (Evidence level I; Randomized Controlled Trials) comparing efficacy and safety of anti-programmed cell death-1 (PD1)/programmed cell death ligand 1 (PD-L1) therapies and chemotherapy in the treatment of advanced NSCLC. A search strategy was devised to identify the randomized controlled trials (RCTs) using electronic databases of PubMed, Cochrane Library, and Web of Science. Hazard ratios or odds ratios obtained for overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and treatment related adverse events (TRAEs) were analyzed using fixed effect model or random effects model. Additionally, subgroup analysis was also performed. A total of seven RCTs (n = 3867) were identified and selected for inclusion in this meta-analysis. Anti-PD1/PD-L1 therapies (nivolumab, pembrolizumab, atezolizumab) resulted in better OS (HR 0.72 [95% confidence interval [CI] 0.63, 0.82; P < .00001]), PFS (HR 0.84 [95% CI 0.72, 0.97; P < .02]), and ORR (odds ratio [OR] 1.52 [95% CI 1.08, 2.14; P < .02]) in comparison to chemotherapy in advanced NSCLC. Improved safety was observed with anti-PD1/PD-L1 therapies (OR 0.31 [95%CI 0.26, 0.38; P < .00001]). Subgroups analysis revealed Eastern Cooperative Oncology Group Performance Status (ECOG PS) 1 (HR 0.76 [95%CI 0.62, 0.93; P = .007]), squamous cell type (HR 0.76 [95% CI 0.63, 0.92; P = .005]), current/former smoker (HR 0.76 [95% CI 0.63, 0.92; P = .005]), epidermal growth factor receptor (EGFR) wild type (HR 0.67 [95% CI 0.60, 0.76; P < .00001]), Kirsten rat sarcoma oncogene mutation (KRAS) mutant (HR 0.60 [95% CI 0.39, 0.93; P < .02]), and absence of central nervous system (CNS) metastases (HR 0.71 [95% CI 0.63, 0.80; P < .00001]) were associated with better overall survival. Anti-PD1/PD-L1 therapies are safe and effective treatment option in advanced non-small cell lung cancer and can be recommended selectively.

Background: ALK inhibitors have shown positive advance in the treatment of ALK+ NSCLC. They have achieved better results in prolonging the progression free survival and improving quality of life in comparison to chemotherapy. We have assembled the evidence related to the efficacy and safety of these agents in the treatment of ALK positive NSCLC. Materials and Methods: A comprehensive search was conducted using electronic databases of PubMed, Medline and Cochrane Library to identify the studies involving comparison of ALK inhibitors to chemotherapy and Next generation ALK inhibitors to crizotinib. PFS was the primary outcome while other outcomes like ORR, adverse events, quality of life and OS were also analyzed and compared. Hazard ratios and odds ratios obtained were analyzed using fixed effect or random effects model in Review Manager Software. Results: A total of 12 studies (n = 3,297) met the criteria for inclusion in this review and meta-analysis. ALK inhibitors including crizotinib, ceritinib and alectinib revealed significantly better PFS (HR 0.42 [0.35, 0.50; p < 0.00001]), ORR (Overall OR 6.59 [4.86, 8.94; p < 0.00001] as compared to chemotherapy in the first line as well as second line treatment settings. Intracranial response rate was better with ALK inhibitors (ceritinib and alectinib) as compared to chemotherapy OR 6.51 [2.86, 14.83; p < 0.00001]. No significant increase in grade 3 or 4 adverse events was observed with crizotinib (OR 1.21 [0.82, 1.77; p = 0.34]) or ceritinib (OR 1.49 [0.86, 2.57; p = 0.17]) when compared to chemotherapy individually. Quality of life indicators assessed were significantly improved with ALK inhibitors. Next generation agents (ceritinib, alectinib and brigatinib) revealed significant improvement in PFS (HR 0.50 [0.43, 0.57; p < 0.00001]), ORR (OR 1.57 [1.21, 2.04; p = 0.0006]) in comparison to crizotinib. Next generation agents (Alectinib and brigatinib) yielded better response intra-cranially than crizotinib in terms of objective response rate (OR 5.87 [3.49, 9.87; p < 0.00001]) and time to CNS progression (HR 0.25 [0.13, 0.46; p < 0.0001]). Alectinib by far resulted in fewer adverse events than chemotherapy or crizotinib. Conclusions: Overall ALK inhibitors are safe and effective treatment option in ALK+ non-small cell lung cancer. Of the ALK inhibitors, Next generation agents in particular alectinib and brigatinib are safer and more effective intra-cranially and can be preferred as first option.

Background Current checkpoint immunotherapy has shown potential to control cancer by restoring or activating the immune system. Nevertheless, multiple mechanisms are involved in immunotherapy resistance which limits the clinical benefit of checkpoint inhibitors. An immunosuppressive microenvironment is an important factor mediating the original resistance of tumors to immunotherapy. A previous report by our group has demonstrated that local angiotensin II (AngII) predominantly exists in a tumor hypoxic microenvironment where hypoxic tumour cells produced AngII by a hypoxia-lactate-chymase-dependent mechanism. Results Here, using 4T1 and CT26 syngeneic mouse tumor models, we found that local AngII in the tumor microenvironment was involved in immune escape of tumour cells and an AngII signaling blockage sensitized tumours to checkpoint immunotherapy. Furthermore, an AngII signaling blockage reversed the tumor immunosuppressive microenvironment, and inhibition of angiotensinogen (AGT, a precursor of AngII) expression strongly triggered an immune-activating cytokine profile in hypoxic mouse cancer cells. More importantly, AGT silencing combined with a checkpoint blockage generated an abscopal effect in resistant tumors. Conclusion Our study demonstrated an important role of local AngII in the formation of a tumor immunosuppressive microenvironment and its blockage may enhance tumor sensitivity to checkpoint immunotherapy. The combination of an AngII signaling blocker and an immune-checkpoint blockage could be a promising strategy to improve tumors responses to current checkpoint immunotherapy.

Background: The prognostic role of 18F-fluorodeoxyglucose positron emission tomography CT (18F-FDG PET/CT) parameters is still controversial in nasopharyngeal carcinoma patients. We sought to perform a systematic review and meta-analysis to explore the prognostic value of maximal standardized uptake value (SUVmax), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) on event-free survival (EFS) and overall survival (OS) in nasopharyngeal carcinoma patients.