Investigation on potential biomarkers of hyperprogressive disease (HPD) triggered by immune checkpoint inhibitors (ICIs)

This project aimed to survey the clinical characteristics and survivals of hyperprogressive disease (HPD) mediated by immune checkpoint inhibitors (ICIs) in an attempt to explore the potential predictors.After searching PubMed, MEDLINE, Google Scholar and Cochrane Library databases, 12 studies incorporating 1766 individuals were enrolled. The data were analyzed with Review manager 5.3 software.The results revealed HPD correlated with previous metastatic sites > 2 (OR = 1.86, 95% CI 1.33-2.59, P = 0.0003), liver metastasis (OR = 3.35, 95% CI 2.09-5.35, P < 0.00001), Royal Marsden Hospital (RMH) score ≥ 2 (OR = 2.80, 95% CI 1.85-4.23, P < 0.00001), higher ECOG PS (OR = 1.60, 95% CI 1.13-2.27, P = 0.008) and LDH > upper limits of normal (ULN) (OR = 2.32, 95% CI 1.51-3.58, P = 0.0001). Instead, HPD was unrelated to gender, age, smoking status, PD-L1 expression, therapy, neutrophil-to-lymphocyte ratio, the histology, the status of EGFR, ALK and KRAS in non-small cell lung cancer and HER-2 expression in advanced gastric cancer. Moreover, HPD was evidently correlated with a shorter OS (HR = 2.92, 95% CI 1.79-4.76, P < 0.0001) and PFS (HR = 3.62, 95% CI 2.79-4.68, P < 0.00001). The same phenomena existed in stratified studies based on study regions and tumor types.This study demonstrated that HPD was related to the number of prior metastatic sites > 2, liver metastasis, RMH score ≥ 2, higher ECOG PS score and LDH > ULN. Moreover, HPD was correlated with a poor OS and PFS in patients following ICI therapy.