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Invited Commentary
June 11, 2020

Hyperprogressive Disease After Treatment With Checkpoint Inhibitors: Time for Prospective Studies

Author Affiliations
  • 1Fred Hutchinson Cancer Center, University of Washington, Seattle
JAMA Oncol. 2020;6(7):1046-1047. doi:10.1001/jamaoncol.2020.1633

Immunotherapy, immune checkpoint inhibitors (ICIs) in particular, has dramatically changed the treatment and outcome of patients with many forms of cancer, including non–small cell lung cancer (NSCLC). The mechanism of action of these agents is to exert an antitumor immunity through T cells that have been inhibited by the cancer. The adverse effect profile of these agents is different from that of chemotherapy. Although ICIs are generally well tolerated, around 10% of patients have grade 3 to 5 adverse events associated with immune phenomena related to the agent’s mechanism of action. Since the introduction of ICIs, several groups have reported a paradoxical accelerated tumor progression after the initiation of therapy; in patients with NSCLC, the incidence ranges between 8% and 21%.1 Considerable debate continues regarding whether this is a true phenomenon or merely a function of tumor growth kinetics in a progressing, previously treated cancer. A major challenge to the ability to further study and delineate who is at risk of developing hyperprogressive disease (HPD) is a lack of consensus about how to define it.

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