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Immune checkpoint inhibitor efficacy in opposition to glioblastoma might lower with dexamethasone

Amongst sufferers with glioblastoma receiving an immune checkpoint inhibitor, those that acquired the corticosteroid dexamethasone at baseline for cerebral edema had considerably worse total survival, in line with outcomes of a examine printed in Medical Most cancers Analysis, a journal of the American Affiliation for Most cancers Analysis.

“Dexamethasone is a potent corticosteroid that’s typically prescribed to sufferers with glioblastoma to deal with signs associated to cerebral edema, or swelling within the mind,” stated David A. Reardon, MD, scientific director of the Middle for Neuro-Oncology at Dana-Farber Most cancers Institute in Boston. “Cerebral edema is a typical but doubtlessly life-threatening complication for sufferers with glioblastoma, and therapy with corticosteroids can assist to suppress the irritation within the mind,” he added.

“Traditionally, sufferers with glioblastoma have been empirically handled with dexamethasone, even with out signs, with many clinicians prescribing steroids for extended durations of time, out of a priority that sufferers might begin to develop edema,” Reardon continued. “Our examine was designed to have a look at that paradigm of scientific apply, significantly within the immunotherapy period, and decide if there could possibly be detrimental penalties related to dexamethasone use amongst sufferers with glioblastoma handled with immune checkpoint inhibitors.”

Reardon and colleagues evaluated the impact of concurrent dexamethasone administration with an immune checkpoint inhibitor (anti-PD-1 remedy) in syngeneic murine glioblastoma fashions. In an immunosensitive mouse mannequin, which is inherently conscious of immune checkpoint blockade, the researchers discovered that the addition of dexamethasone to anti-PD-1 remedy resulted in diminished survival in a dose-dependent method. Moreover, in an immunoresistant mouse mannequin, which Reardon famous is extra consultant of human glioblastoma, the addition of dexamethasone to anti-PD-1 remedy or anti-PD-1 remedy plus radiotherapy additionally resulted in diminished survival.

“In our preclinical research, we discovered that steroids had a big detrimental impact on the efficacy of anti-PD-1 remedy, even in an immunosensitive mannequin, which over-predicts the good thing about immune checkpoint blockade in glioblastoma sufferers,” stated Reardon.

The researchers subsequent analyzed total survival information from 181 sufferers with glioblastoma handled with both anti-PD-1 or anti-PD-L1 remedy at Dana-Farber Most cancers Institute who have been recognized earlier than April 1, 2019. This affected person inhabitants was heterogeneous, with sufferers receiving therapy by a scientific trial or on a compassionate use foundation; roughly 76 % have been handled for recurrence, and roughly 24 % have been handled for a brand new prognosis. Of those 181 sufferers, round 35 % have been taking dexamethasone at baseline.

Reardon and colleagues evaluated the potential detrimental impact of dexamethasone utilizing multivariable evaluation, the place they adjusted for quite a lot of elements, together with illness setting (newly recognized versus recurrent), tumor quantity at therapy initiation, age, and extent of resection, among the many 163 sufferers that had full annotated information for related prognostic elements. In contrast with sufferers who weren’t taking dexamethasone at baseline, sufferers handled with dexamethasone had roughly twice the chance of demise. Additional, baseline use of dexamethasone was the strongest recognized detrimental danger issue for total survival.

“Our outcomes recommend that we should always attempt to keep away from dexamethasone amongst sufferers with glioblastoma who’re handled with immunotherapy, and if corticosteroids are clinically required, we should always use these medication judiciously,” Reardon stated. “Additional, our outcomes spotlight that different methods for the therapy of cerebral edema that don’t have such a broad anti-inflammatory impact critically have to be investigated.”

Limitations of the examine embrace the retrospective nature of the scientific analyses. Additional, of their preclinical research, the researchers solely evaluated the impact of dexamethasone on the efficacy of anti-PD-1 therapy. “Whether or not the identical observations would happen with different immunomodulatory checkpoint focusing on brokers, and even different immunotherapy remedies—comparable to vaccines, adoptive mobile therapies, or genetically engineered oncolytic viruses—stays to be evaluated,” Reardon stated.

This examine was sponsored by The Jennifer Oppenheimer Most cancers Analysis Initiative; The Ben and Catherine Ivy Basis; Hope It is A Seashore Factor, an annual 5K for mind tumor analysis; and the Pan- Mass Problem, a bike-a-thon that raises cash for the Dana-Farber Most cancers Institute. This examine was additionally funded by the Nationwide Institutes of Well being.

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Extra info:
Medical Most cancers Analysis (2020). DOI: 10.1158/1078-0432.CCR-20-2291

Offered by
American Affiliation for Most cancers Analysis

Immune checkpoint inhibitor efficacy in opposition to glioblastoma might lower with dexamethasone (2020, November 25)
retrieved 25 November 2020

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