This article is more than 5 years old. Information may no longer be current.
Hyperprogressive disease not associated with treatment-related toxicities during immunotherapy
Click Here to Manage Email Alerts
Hyperprogressive disease did not appear to be related to clinically significant adverse events, age, tumor type or type of immunotherapy among patients with solid tumors in early-phase trials, according to results of a retrospective study published in Cancer.
Overall, 7% of patients treated in these trials experienced hyperprogressive disease, which appeared more common among women than men, results showed.
“Growth kinetics can be variable [and] immunotherapy introduced the concept of treating beyond radiographic progression because of the possibility of pseudoprogression or immune flare,” Philippe L. Bedard, MD, FRCPC, assistant professor of medicine at University of Toronto and fellowship director for the Bras Family New Drug Development Program at Princess Margaret Cancer Centre, told HemOnc Today. “This has also raised awareness of the possibility that a small minority of patients may experience accelerated tumor growth during immune checkpoint inhibitor therapy.”
Previous studies have demonstrated that a subset of patients treated with checkpoint inhibitors experience an accelerated tumor growth rate, known as hyperprogressive disease.
Bedard and colleagues specifically studied the relationship between hyperprogressive disease and treatment-related toxicity and clinical factors among 182 patients (median age, 60 years; 54% women) with solid tumors treated in early-phase immunotherapy trials at Princess Margaret Cancer Centre in Canada. The most common cancer types were head and neck (18%), gynecological (16%), lung (15%), gastrointestinal (15%) and genitourinary (12%). Patients had ECOG performance scores of 0 (32%) or 1 (68%).
Eighty percent of patients (n = 146) received a single-agent immunotherapy — primarily PD-1 or PD-L1 inhibitors — and 20% received combination immunotherapies.
Researchers defined hyperprogressive disease as progression by Response Evaluation Criteria in Solid Tumors version 1.1 criteria at first on-treatment scan and a twofold or greater increase in tumor growth rate between the reference (pre-immunotherapy) and experimental periods. Clinically significant adverse events included treatment-related toxicities requiring systemic therapy, drug delays or discontinuation.
Twelve patients (7%) experienced hyperprogressive disease. Ten of these patients were women (P = .01), which researchers deemed an “intriguing” finding that needs to be validated in a larger cohort. However, researchers observed no correlation between hyperprogressive disease and age, performance, tumor type, RMH prognostic score, combination immunotherapy or clinically significant adverse events.
The 1-year OS rate was 28% for patients with hyperprogressive disease and 53% for patients without hyperprogressive disease (HR = 1.7; 95% CI, 0.9-3.3).
Researchers acknowledged limitations to their study, including use of RECIST target lesion measurements to calculate tumor volume as well as the retrospective and nonrandomized design and small cohort size.
“The numbers are too small to make any definitive conclusions,” Bedard said. “Our observation is hypothesis-generating and should be tested in other cohorts.”
With checkpoint inhibitors moving to the frontline of treatment, the opportunity to identify and study hyperprogressive disease will be challenged, Sanjay Popat, PhD, of the department of medicine at Royal Marsden Hospital in London, wrote in an accompanying editorial.
“There are still many questions concerning [hyperprogressive disease], including why it occurs, whether its identification is simply a lead-time bias phenomenon or there is a strong biological basis such as clonal selection, whether we can predict those in whom it will occur, and whether it can be stopped by additional therapies,” Popat wrote. – by John DeRosier
For more information:
Philippe L. Bedard, MD, FRCPC, can be reached at Princess Margaret Cancer Centre, University Health Network, 700 University Ave., 7-723, Toronto, ON, Canada M5G1Z9;
philippe.bedard@uhn.ca.
Disclosures: Bedard reports research funding from AstraZeneca, Bristol-Myers Squibb, Genentech/Roche, GlaxoSmithKline, Immunomedics, Merck, Mersana, Nektar, Novartis, PTC Therapeutics, Sanofi, Seattle Genetics, Servier and SignalChem. Please see the study for all other authors’ relevant financial disclosures. Popat reports research funding from Health Research Biomedical Research Centre at Royal Marsden Hospital.
Click Here to Manage Email Alerts