Atypical patterns of response and progression in the era of immunotherapy combinations

In the immunoncology era, an acceleration of tumor growth upon immune checkpoint inhibitors (ICI), defined as hyperprogressive disease (HPD) has been observed across different cancers. Although in non-small-cell lung cancer, most of the available evidence regarding HPD has been reported for patients treated with single agent PD-1 and PD-L1 inhibitors, in retrospective series a variable proportion of patients receiving ICI combinations also experienced HPD. Similarly, the shape of survival curves and the progression rates in clinical trials testing combinations of PD-1/PD-L1 inhibitors and anti-CTLA-4 agents suggest the occurrence of HPD. Few data are available regarding pseudoprogression upon ICI combinations. However, considering that pseudoprogression has been reported for anti-PD-1/PD-L1 agents and for CTLA-4 inhibitors separately, it is likely that it may occur also upon combinations of these two classes of drugs.