How to recognize and manage hyper-progression and pseudo-progression during immune checkpoint blockade in non-small cell lung cancer

Francesco Facchinetti, Giuseppe Lo Russo, Marcello Tiseo, Marina Chiara Garassino, Roberto Ferrara


The field of immunotherapy for non-small cell lung cancer (NSCLC) patients is in constant evolution, given that combinatorial treatment strategies flank anti-PD-1/PD-L1 monotherapy and disease settings beyond the advanced one derive benefit form immune checkpoint blockers (ICB). In this evolving scenario, the clinical experience derived from advanced NSCLC patients receiving single agent ICB will likely retain relevant meaning. In particular, treatment with PD-1/PD-L1 agents has been accompanied by the emergence of new patterns of clinico-radiological disease response, namely hyper-progression and pseudo-progression. Still harboring different prognostic implications, these two entities share some pathogenetic elements (both involving a dysregulated immune response) and, more importantly, the complexity of recognition and management. In this overview, we gather the evidence on the peculiar characteristics of hyper-progression and pseudo-progression in NSCLC. We aim to provide elements of current and future clinical interest and, moreover, to point out the relevance of getting more pathological and biological insights in these two entities, in order to improve their successful prediction and management.