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Hyperprogression Emerges in a Subset of Patients Treated With Immunotherapy

Published: Monday, Jan 15, 2018
lung cancer
The extent of hyperprogressive disease (HPD) after immunotherapy treatment has not been fully characterized, but evidence continues to build that it may not be as rare of a phenomenon as previously thought. Results from a recent multicenter, retrospective analysis of 242 patients with advanced non–small cell lung cancer (NSCLC) found that 16% developed hyperprogression during anti–PD-1/PD-L1 treatment.1 The study, which was presented at the 2017 ESMO Annual Congress, is among the latest to highlight the risk of hyperprogression.

Awareness of hyperprogression—a rapid increase in tumor growth after initiation of immunotherapy—has been increasing since a 2016 French study first defined hyperprogression in a population of patients receiving anti–PD-1/PD-L1 therapy for melanoma, lung, renal, colorectal, head and neck, breast, brain, cervical, endometrial, and other cancers.2 That study, which was published in Clinical Cancer Research, identified hyperprogression in 12 of 131 patients, for an incidence of 9%. Additional research studies suggest that rapid tumor growth during immunotherapy is likely more common than that, particularly in certain patient populations.

Understanding the definition, incidence, and pathogenesis of hyperprogression will ultimately help clinicians provide better care to patients with cancer. “We know that immunotherapy doesn’t work for everyone. We need to do better,” said Charu Aggarwal, MD, MPH, an assistant professor of hematology/oncology in the Perelman School of Medicine at the University of Pennsylvania, who was instrumental in opening phase I clinical trials of pembrolizumab (Keytruda) in lung cancer at her institution. A key part of “doing better,” she said, will be learning how to accurately identify which patients are likely to benefit from immunotherapy, and which are not.

Hyperprogression Defined

The French study described HPD as a Response Evaluation Criteria in Solid Tumors (RECIST) progression at the first evaluation and a 2-fold or greater increase in tumor growth rate from baseline (before treatment with immunotherapy).2 Similarly, an Annals of Oncology article from April 2017 about hyperprogression during anti– PD-1/PD-L1 therapy in patients with head and neck cancer defined hyperprogression as a tumor growth kinetics ratio equal to or greater than 2 (Figure).3


Figure. Tumor Growth Kinetics of Hyperprogressors Following Immunotherapy

Tumor Growth Kinetics
And an August 2017 study by Shumei Kato, MD; Razelle Kurzrock, MD; and colleagues, used a 3-point definition of hyperprogression4 :
  1. Time-to-treatment failure (TTF) of less than 2 months
  2. Greater than 50% increase in tumor burden compared with preimmunotherapy imaging
  3. Greater than or equal to a 2-fold increase in progression pace
“It’s important to not only compare imaging from right before immunotherapy and after immunotherapy, but to also compare with scans taken about 2 to 3 months before, to look at the pace of progression,” said Kato, an assistant clinical professor of medicine at the University of California, San Diego (UCSD) School of Medicine. Kurzrock is the chief of the Division of Hematology and Oncology, senior deputy director of clinical science, and director of the Center for Personalized Cancer Therapy and Clinical Trials Office at UCSD. Patients who exhibit hyperprogression may have relatively slow or stable tumor growth prior to immunotherapy treatment, followed by a rapid increase in tumor © BIOLOGY PICS / SCIENCE SOURCE. size after initiation of immunotherapy.

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Online CME Activities
TitleExpiration DateCME Credits
Community Practice Connections™: Oncology Best Practice™ Decision Points in Advanced NSCLC: Assessing Treatment Options Beyond Disease ProgressionNov 30, 20181.0
Community Practice Connections™: Precision Medicine for Community Oncologists: Assessing the Role of Tumor-Testing Technologies in Cancer CareNov 30, 20181.0
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