Pooled analysis of hyperprogression with ICIs versus placebo for malignancies in phase 3 studies

Retrospective studies have suggested a potential risk of hyperprogressive disease (HPD) in patients receiving immune checkpoint inhibitors (ICIs). However, these analyses have been subject to a range of limitations, including use of various definitions of HPD. Analyses of two phase 3 randomized, placebo-controlled trials across two tumor types allowed tumor growth in patients receiving nivolumab with or without ipilimumab to be compared with natural tumor progression in the absence of treatment. Evaluation of HPD using a definition based on percentage change from baseline in target lesions sum of the longest diameters across multiple cut-offs showed that neither in ATTRACTION-2 nor in CheckMate 451 ICI treatment was not associated with an increased incidence of disease progression. The authors conclude that reports of rapid tumor growth in patients treated with ICIs may reflect the natural course of disease in some patients. Nivolumab-based treatment is not associated with HPD in the investigated tumor types (GC/GEJC and ED SCLC).