Reply to "Guarantee‐time bias in studies on the relationship between immune‐related adverse events and antitumor activity".

Although further testing in larger series will potentially verify or refute the concerns raised by Cheung et al, we believe that there is a strong biological rationale as well as sufficient data to support the validity of immune-related adverse events (irAEs) as biomarkers of immunotherapy efficacy as signaled in our retrospective series.1 A few considerations that we would like to highlight include the following: Cheung et al appropriately make a comparison with acneiform rash for epidermal growth factor receptor (EGFR) inhibitors and point out that the early appearance of rash largely abrogates the risk for guarantee-time bias. Real-world efficacy and safety of nivolumab in previously-treated metastatic renal cell carcinoma, and association between immune-related adverse events and survival: the Italian expanded access program. Immune-related adverse events are associated with improved response, progression-free survival, and overall survival for patients with head and neck cancer receiving immune checkpoint inhibitors. [Extracted from the article]