DEFINITION OF HYPERPROGRESSION

In non-small-cell lung cancer patients on immunotherapy, a new definition, based on the difference between the tumor growth rate (TGR) before and during therapy, may more accurately define hyperprogressive disease (HPD) than the five current definitions, researchers say.

"We applied the different definitions and noted that they did not give the same prevalence of HPD (which was expected) but surprisingly, they did not identify the same patients," Dr. Caroline Caramella of Paris-Saclay University in Villejuif told Reuters Health by email. "We tested different models in order to identify the worst tumor growth leading to the worst overall survival."

"We then proposed a definition based on a difference in TGR before and during therapy of more than 100," she said. "But we are still cautious - this definition would need to be confirmed and/or refined through new studies and external validations."

As reported in JAMA Oncology, the team's retrospective cohort study included 406 patients with advanced NSCLC treated with PD-1/PD-L1 inhibitors from 2012-2017 in eight French institutions. Patients' median age at the start of immune checkpoint inhibitor treatment was 64, and 64% were men.

Measurable lesions were defined using the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria on at least two computed tomographic scans before therapy initiation and one scan during treatment.

The different definitions resulted in HPD incidences that varied from 5.4% with a definition based on a >2-fold progression pace and a time to treatment failure of <2 months, to 18.5% based on a definition of the TGR ratio.

Concordance among the different definitions varied from 33.3% to 69.3%. However, for every definition, HPD was associated with poorer survival - i.e., range of median overall survival, 3.4 to 6.0 months.

The new definition - an optimal threshold of a difference in TGR before and after therapy of more than 100 - correlated most with poor overall survival, with an initial plateau for a larger number of patients and a slower increase; it also had the highest ability to distinguish patients with HPD from those with progressive disease not classified as HPD.

As Dr. Caramella noted, more studies on larger groups of patients are needed to validate the proposed definition.

Medical oncologist Dr. Kevin Sullivan of the Northwell Health Cancer Institute in Lake Success, New York, told Reuters Health, "I agree with the researchers that current definitions of HPD make it difficult to fit neatly into one characterization. Their findings certainly confirm that HPD is a rare phenomenon and I think their classification is helpful," he said by email.

"However," he noted, "whether a patient experiences HPD or what is more commonly seen as general disease progression without this phenomenon of 'hyperprogression,' if the patient is not responding to a particular therapy, it indicates that a change in treatment is warranted, or a shift in overall management to...symptom management alone - in the setting of hospice, for example."

"Ultimately, recognizing when a patient's cancer is worsening and whether or not a patient is a candidate for further treatment depends upon astute clinical skills and a good doctor-patient relationship," he concluded.

Dr. Ankur Parikh, Precision Medicine Program Director at Cancer Treatment Centers of America in Philadelphia, told Reuters Health by email, "While I agree their definition utilizing change in TGR of greater than 100 may identify a more at-risk population, this is a retrospective study reviewing non-small cell lung cancers only. The other definitions listed are based on studies done in various cancers."

"Larger prospective studies looking at specific tumor types, tumor genomics and more standard imaging would help assess the validity of the new HPD definition," he said. "This article highlights the challenges and complexities clinicians face and the significant need to identify the specific patient populations that will fare worse by receiving treatment with immune checkpoint inhibitors."

SOURCE: https://bit.ly/2N99Rm0 and https://bit.ly/37E9qcR JAMA Oncology, online June 11, 2020.