The definition of hyperprogressive disease (HPD) in advanced non–small cell lung cancer (NSCLC) was found to vary widely, yielding “highly variable” rates of HPD, a study published in JAMA Oncology found. HPD is a controversial phenomenon in which dramatic tumor growth occurs following the initiation of immune checkpoint inhibitor therapy.

The study authors evaluated 5 definitions of HPD by applying each definition to a retrospective cohort of 406 patients from 8 centers in France who had advanced NSCLC and received programmed cell death-1 (PD-1)/programmed cell death-1 ligand (PD-L1) inhibitors from November 1, 2012, to April 5, 2017.

The different definitions revealed varying incidences of HPD in the study population. As little as 5.4% of the study population had HPD according to one definition, while another definition identified a much higher rate of 18.5%.

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The conservative incidence of 5.4% was based on an HPD definition that required 3 conditions to be met: time to treatment failure of less than 2 months, Response Evaluation

Criteria in Solid Tumors (RECIST) percentage of more than 50%, and progression pace of more than 2-fold.

The high incidence of 18.5% was based on an HPD definition based on the use of tumor growth kinetics, “which does not account for the hypothesis of the natural exponential growth of the tumor and uses the diameters rather than the volume,” according to the study authors.

The definitions also had varying levels of concordance, ranging from 33.3% to 69.3% — but  each was consistently linked to poor survival, ranging from a median overall survival (OS) of 3.4 months (95% CI, 1.9-8.4 months) to 6 months (95% CI, 3.7-9.4 months).

“The choice of the definition seems therefore to be a major reason for the diversity

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observed among previous studies,” the study authors wrote. “Beyond the question of incidences, these results also highlight the fact that the groups of patients with HPD appear to differ from one definition to the other, with only 19 patients being common to all definitions.”

The study authors proposed a new definition for HPD, the criteria being: a change in tumor growth rate of more than 100, RECIST percentage of more than 20%, and association with poor OS outcomes.


Kas B, Talbot H, Ferrara R, et al. Clarification of definitions of hyperprogressive disease during immunotherapy for non-small cell lung cancer [published online June 11, 2020]. JAMA Oncol. doi: 10.1001/jamaoncol.2020.1634