Hyperprogressive Disease in Advanced Cancer Patients Treated with Nivolumab: a Case Series Study

The aim of this retrospective study was to detail the main clinicopathological characteristics of advanced cancer patients exhibiting hyperprogressive disease (HPD) during immune checkpoint inhibitor (ICI) nivolumab as second- or third-line treatment. A cohort of patients starting second or third-line nivolumab for advanced cancer from 2016 to 2018 was identified from our institution IRB approved and prospectively collected registry. HPD was defined as at least two-fold increase in the tumor growth rate (TGR) during immunotherapy compared to TGR during the preimmunotherapy period. Overall, 47 patients were eligible for this analysis. HPD was observed in three patients (6%) with metastatic lung adenocarcinoma, metastatic urothelial transitional carcinoma, and metastatic hepatocellular carcinoma, respectively. These three patients showed a rapid clinical deterioration and survived less than 3.5 months from immunotherapy onset. Their chief preimmunotherapy characteristics were: age < 75 years, ≥2 metastatic sites, programmed death-ligand 1 < 50%, neutrophil-to-lymphocyte ratio > 3, and elevated lactate dehydrogenase. The results of the current study seem to reinforce the hypothesis that in some cases immunotherapy promotes a dramatic increase of TGR and may suggest possible clinical predictors of HPD during nivolumab.