Initial data suggest that tumors harboring high levels of somatic mutations might be highly sensitive to ICIs.22, 23 Our meta\analysis showed that ICIs represented an effective treatment routine for individuals with a high TMB, irrespective of PD\L1 manifestation level. of ineligible studies, 12 eligible randomized controlled trials were included. Data showed that ICIs significantly improved progression\free survival (HR 0.66, 95% CI 0.57C0.77, 0.00001), overall survival (HR 0.77, 95% CI 0.64C0.91, = 0.003), and but not objective response rate (RR 1.97, 95% CI 1.25C3.13, = 0.004) in all unselected NSCLC populations. However, they failed to increase the OS of programmed death\ligand 1 = 1C49% subgroup (HR 0.78, 95% CI 0.51C1.19, = 0.25) and PFS of programmed death\ligand 1 1% subgroup (HR 0.85; 95%CI 0.70 to 1 1.03, 0.05 was considered to show statistical significance. Level of sensitivity analysis was carried out by excluding one study at a time and also by removing one study with the highest weightage, among the included data to examine the influence of bias within the deduced statistical significance and interpretation. Risk ratios were determined for AEs at 95% CIs. Results Results of search Using the search strategy, we originally retrieved 1015 records from our database search. Among these, 86 content articles were excluded for duplication, and 884 content articles were excluded by screening the title and abstract. After cautiously reading the full texts of the remaining 45 content articles, six eligible studies21, 25, 26, SS-208 27, 28, 29 met the inclusion criteria. Five abstracts30, 31, 32, 33, 34, 35 were included from your American Society of Clinical Oncology conference proceedings. The part publication of four American Society of Clinical Oncology abstracts were published after the literature search date and have been included instead. One additional study36 was recognized through manual searches in 2018 AACR. Our selection process and reasons for study exclusion are demonstrated in Number ?Figure11. SS-208 Open in a separate windowpane Number 1 Study recognition and selection process. AACR, American Association for Malignancy Study; ASCO, American Society of Clinical Oncology. Characteristics of the qualified studies These 12 eligible studies were all published between 2010 and 2018. Of the 12 studies enrolled, three28, 30, 34 were carried out in patients with SQ NSCLC, three27, 29, 36 in SS-208 those with non\SQ NSCLC, and the other six21, 25, 26, 31, 32, 33, 35 were carried out in all subtypes of NSCLC. A total of 1021, 25, 28, 29, 30, 32, 33, 34, 35, 36 phase III and two26, 27 phase II randomized clinical trials were considered eligible for the meta\analysis. A total of 8384 patients (ICIs: 3842; chemotherapy: 3120) were included in the analysis from five25, 27, 30, 33, 36 pembrolizumab trials, three21, 32, 35 nivolumab trials, two29, 34 atezolizumab trials, and two26, 28 ipilimumab trials. The detailed characteristics of the 12 studies are offered in Table ?Table11. Table 1 Characteristics of the 12 randomized controlled trials comparing immune checkpoint inhibitors chemotherapy with chemotherapy placebo 66 (38C85)92,59.7% vs. 95,62.9%AnyPD\L1 50%Pembrolizumab 200 mg Q3W vs. chemotherapy305Lopes = 0.003), whereas no significant difference in OS for ICIs alone over chemotherapy (Fig. ?(Fig.3a;3a; HR 0.82, 95% CI 0.68C1.00, = 0.06). Table 2 Overall survival and progression\free survival in the 12 randomized controlled trials comparing immune checkpoint inhibitors chemotherapy with chemotherapy placebo 0.00001), nevertheless. For anti\PD\1/PD\L1 monotherapy, no positive result in PFS was obtained when compared with chemotherapy Rabbit polyclonal to Argonaute4 (Fig. ?(Fig.3a;3a; HR 0.70, 95% CI 0.39C1.26, = 0.24). Many studies SS-208 included in this meta\analysis also reported the partial or complete overall response rate according to RECIST (version 1.1). We compared the overall response rate of ICIs therapy with chemotherapy for advanced NSCLC patients. The pooled OR for the overall response rate (ORR) in the ICIs arm over the chemotherapy arm experienced no significant differences (Fig. ?(Fig.3a3a in ICIs vs. chemotherapy: OR.