Database Selection and Heterogeneity—More Details, More Credibility—Reply

In Reply We appreciate the interest and comments by Li and colleagues regarding our article, which compared the incidence of endocrine adverse events following treatment with immune checkpoint regimens in a systematic review and meta-analysis of published trial reports. Our work included a total of 38 clinical trials retrieved from the PubMed database evaluating the use of checkpoint inhibitors for the treatment of advanced solid tumors, resulting in a total of 7551 patients who were eligible for this meta-analysis. Thus, it is unlikely that the data regarding the incidence of thyroid toxic effects or hypophysitis would differ significantly if further studies were added. We recognize that after the date of the database search (July 18, 2016), new articles have been published, and an update of our work with new studies and additional information sources would be welcome. By including newly reported clinical trials, such efforts may help to establish the incidence and risks of less frequent endocrinopathies, such as primary adrenal insufficiency and type 1 diabetes. Moreover, in our meta-analysis we did not include other types of immunotherapy combination regimens, such as programmed cell death/programmed cell death ligand 1 inhibitors plus chemotherapy or combinations with antiangiogenic drugs. A work including these regimens would be of interest now that some combinations have been approved, and many are under review for approval, for the treatment of different advanced solid tumors.

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