Several irAEs are late-onset [3C8], appearing after the confirmation of objective response, which might result in lower relativity. of irAEs and their correlations with objective response rate (ORR) in patients with advanced solid tumours treated with nivolumab (NIVO) or nivolumab plus ipilimumab (NIVO+IPI). Methods PubMed, Embase and Cochrane library were searched for Osthole eligible studies from January 1st, 2000 to May 1st 2019. Published clinical trials on NIVO or NIVO+IPI with reported irAEs were included. Logit transformation of the irAE incidences was applied for the generation of pooled estimate and Pearson correlation coefficient was calculated to evaluate the correlation between irAE and ORR. Results 48 clinical trials including 7936 patients treated with NIVO or NIVO+IPI were included. Compared to NIVO, NIVO+IPI led to more all-grade and grade 3 or higher irAEs categorized by system organ class ( em P /em ? ?0.05). The ORR of NIVO was positively correlated with the incidence rate of skin (r?=?0.79, em P /em ? ?0.001), gastrointestinal (r?=?0.56, em P /em ?=?0.006) and endocrine irAEs (r?=?0.44, em P /em ?=?0.05), but not hepatic, pulmonary and renal irAEs. The ORR of NIVO+IPI was positively correlated with the incidence rate of skin (r?=?0.54, em P /em ?=?0.04), and gastrointestinal irAEs (r?=?0.60, em P /em ?=?0.02), but not endocrine, hepatic, pulmonary and renal irAEs. Conclusion This meta-analysis summarizes the incidence rates of irAEs in patients with advanced solid tumours treated with NIVO or NIVO+IPI, and uncovers their correlations with ORR across multiple neoplasms. These findings spotlight the potential of irAE to reflect response to NIVO or NIVO+IPI. strong class=”kwd-title” Keywords: Immune-related adverse events, Meta-analysis, Nivolumab, Ipilimumab Introduction For the past decades, immunotherapy by targeting programmed cell death-1 (PD-1), programmed cell death-ligand 1 (PD-L1), or cytotoxic T lymphocyte associated antigen 4 (CTLA-4) has revolutionized the treatment of malignancy. Among these regimens, nivolumab monotherapy (NIVO) or nivolumab plus ipilimumab (NIVO+IPI) have been approved by the US Food and Drug Administration for indications including advanced lung malignancy, melanoma, renal cell carcinoma (RCC), head and neck squamous cell carcinoma (HNSCC), hepatocellular carcinoma (HCC), urothelial carcinoma, colorectal carcinoma (CRC) and classical Hodgkin lymphoma. Despite the impressive anti-tumour activity by removing the barrier of immune checkpoint, anti-PD-1/PD-L1 and anti-CTLA-4 reactivate the T cell-mediated anti-tumour immunity, and in the mean time, inevitably break the innate immuno-homeostasis via facilitating the Osthole loss of immune tolerance to autoantigens [1], which is usually associated with the generation of adverse events, known as immune-related adverse events (irAEs). IrAEs are varied in terms of tissues affected, the severity, and the time of onset relative to the initiation of treatment [2C8]. Numerous clinical trials have layed out a crude profile Osthole of irAEs, including skin, gastrointestinal, pulmonary, hepatic, endocrine and renal toxicities [1, 9]. The most common irAEs include pruritus, rash, nausea, diarrhea and thyroid disorders [9]. Rabbit Polyclonal to ARC The vast majority of these irAEs develop within the first few weeks to months after treatment initiation, while others like liver toxicity or hypophysitis appear later [1, 10]. Most irAEs are moderate to moderate, except some are potentially fatal, e.g., Osthole colitis, pneumonitis, hepatitis, myocarditis, and neurotoxic effects [11]. Hence, there is an urgent need to be acquainted with the toxicological profile. A recent meta-analysis including 125 clinical trials, provides a comprehensive profile for the irAEs of single-agent immunotherapy [12]. However, this meta-analysis merely provided the pooled estimate of irAEs from all anti-PD-1/PD-L1 monotherapy, without announcing the specific data for each one and comparing the difference among these brokers. In addition, severer irAEs owing to the combination with anti-CTLA-4 worth more consciousness [12], and thus the incidence rates of irAEs for NIVO and NIVO+IPI are of great vitality and remain to be analyzed. Not only do irAEs belong to side effects that require rigorous care, they also serve as windows into the anti-tumour response of ICIs. The association between irAEs and survival of patients treated with NIVO was first reported in melanoma. In 148 patients with melanoma treated with NIVO, irAEs were associated with better OS Osthole using a 12-week landmark [13]. Recent studies have also exhibited that in non-small cell lung malignancy (NSCLC) treated with NIVO, the patients with irAE occurring within 6?weeks post treatment, reached longer progressive-free survival (PFS) and overall survival (OS) than those without irAE [14]. However, irAEs of different organs vary in severity and time of onset [2C8]. The irAEs of grade 3 or 4 4 according to CATAE v4.0 demand extra usage.