In Reply We thank Conner and Trinquart for their interest in our study1 on the association between preexisting antibodies and anti–PD-1 (programmed cell death 1) therapy. We agree that it is important to use landmark analysis in the assessment of an association between early immune-related adverse events (irAEs) and survival.
However, the primary aim of the study was to assess the safety and efficacy of anti–PD-1 treatment in patients with subclinical disease with advanced non–small cell lung cancer and with or without preexisting autoimmune markers, including rheumatoid factor, antinuclear antibody, antithyroglobulin, and antithyroid peroxidase.1 We also sought to assess potential clinical biomarkers that may be meaningfully and conveniently associated with clinical benefit or with irAEs following anti–PD-1 treatment. In the study, we presented the Kaplan-Meier curves for the relationship between irAEs and survival; however, the aim was not to evaluate whether early-onset irAEs are a predictor of therapeutic effect. It would be natural for the development of irAEs to increase as survival continues, and late-onset irAEs may develop in long-term responders. We believe that cautious management of irAEs can permit the maximum clinical benefit from anti–PD-1 antibody therapy regardless of early- vs late-onset irAEs.