Although existing evidence from clinical trials has demonstrated manifestation of hepatic adverse events with the use of immune checkpoint inhibitors (ICPIs), overall risks have yet to be reported. Therefore, we assessed the risk of hepatotoxicity associated with inhibitors of the immune checkpoint. We examined data from the Pubmed, Medline and Google Scholar databases. We also examined original studies and review articles for crossreferences Eligible studies included randomized Phase II to Phase III trials of cancer patients treated with nivolumab, pembrolizumab, ipilimumab, tremelimumab. The authors extracted relevant information on participants' characteristics, all-grade and high-grade hepatotoxicity and information on the methodology of the studies. In total, 17 trials were considered eligible for the meta-analysis. The odds ratio for all-grade hepatotoxicity for CTLA-4 inhibitors (Ipilimumab and tremelimumab) was 1.24 (95% confidence interval 0.75, 2.05; p = 0.39) and for high-grade hepatotoxicity was 1.93 (95% confidence interval 0.84, 4.44; p =0.12). Moreover, the odds ratio for all-grade hepatotoxicity for PD-1 inhibitors was 1.52 (95% confidence interval 1.24, 1.86; p < 0.0001) and for high-grade hepatotoxicity was 0.48 (95% confidence interval 0.29, 0.80; p =0.005). The analysis of data showed that CTLA-4 inhibitors seem to be associated with a higher risk of all- and high-grade hepatotoxicity compared with control regimens, whereas PD-1 inhibitors seem to be associated with a lower risk of all- and high-grade hepatotoxicity compared with control regimens.

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Previous studies of irinotecan pharmacogenetics have shown that the UGT1A1*28 polymorphism has an effect on irinotecan (IRI)-induced toxicities in Caucasians. Yet compared with the UGT1A1*6 mutation, the UGT1A1*28 occurs at a much lower frequency in the Asians. Whether UGT1A1*6 and UGT1A1*28 are associated with IRI-induced neutropenia, diarrhea and IRI-based chemotherapy tumor response (TR) in Asians with lung cancer remains controversial. In this meta-analysis, we found a higher risk of neutropenia and diarrhea with IRI-based chemotherapy in Asians with lung cancer carrying the UGT1A1*6 polymorphism. However, UGT1A1*28 showed a weak correlation with diarrhea, but no significant correlation with neutropenia. Neither UGT1A1*6 nor UGT1A1*28 is associated with IRI-based chemotherapy TR. These data suggest that the UGT1A1*28 polymorphism may not be a suitable biomarker to predict IRI-induced toxicities and chemotherapy TR in Asians, while UGT1A*6 polymorphism is associated with a higher risk of IRI-induced neutropenia and diarrhea, but not IRI-based chemotherapy TR.

Background: It has been confirmed that epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) presented better efficacy than brain radiotherapy (brain RT) in the treatment of brain metastasis (BM) in EGFR mutated NSCLC patients. However, whether the combination of EGFR-TKIs and brain RT is better than EGFR-TKIs alone remains unclear. We aim to compare the outcomes of adding brain RT to EGFR-TKIs and to screen for the beneficial population by a meta-analysis of currently available data. Methods: A systematic search for relevant articles was conducted in six databases. The outcomes were overall survival (OS) and intracranial progression-free survival (iPFS) between groups, both were measured as hazard ratios (HRs). Meta-regression and dominant subgroup analysis were used to explore advantageous subgroups. Results: A total of 12 retrospective studies involving 1,553 EGFR mutated patients with BM at the first diagnosis were included. EGFR-TKIs plus brain RT showed a significant prolonged OS (HR =0.64, 95%