Hyperprogression and Immune Checkpoint Inhibitors: Hype or Progress?

The oncologist

article

Jacob J. Adashek¹  Shumei Kato²  Roberto Ferrara³  Giuseppe Lo Russo³  Razelle Kurzrock² 

[1] Department of Internal Medicine, University of South Florida, H. Lee Moffitt Cancer Center & Research Institute;Center for Personalized Cancer Therapy and Division of Hematology and Oncology, Department of Medicine, University of California San Diego Moores Cancer Center;Thoracic Oncology Unit, Department of Oncology, Fondazione I.R.C.C.S. Istituto Nazionale dei Tumori

关键词: Hyperprogressive disease;    Immunotherapy;    Cancer clinical trials;    Immune checkpoint inhibitors;   

DOI  :  10.1634/theoncologist.2019-0636

学科分类：地质学

来源: AlphaMed Press Incorporated

【 摘 要 】

There are currently seven approved immune checkpoint inhibitors (ICIs) for the treatment of various cancers. These drugs are associated with profound, durable responses in a subset of patients with advanced cancers. Unfortunately, in addition to individuals whose tumors show resistance, there is a minority subgroup treated with ICIs who demonstrate a paradoxical acceleration in the rate of growth or their tumors—hyperprogressive disease. Hyperprogressive disease is associated with significantly worse outcomes in these patients. This phenomenon, though still a matter of dispute, has been recognized by multiple groups of investigators across the globe and in diverse types of cancers. There are not yet consensus standardized criteria for defining hyperprogressive disease, but most commonly time to treatment failure less than 2 months and an increase in pace of progression of at least twofold between pre-immunotherapy and on-treatment imaging has been used. In some patients, the change in rate of progression can be especially dramatic—up to 35- to 40-fold. MDM2 amplification and EGFR mutations have been suggested as genomic correlates of increased risk of hyperprogression, but these correlates require validation. The underlying mechanism for hyperprogression is not known but warrants urgent investigation.

【 授权许可】

CC BY|CC BY-NC