Sex disparity identified for hyperprogressive disease after immunotherapy
medwireNews: Women may be at greater risk than men for experiencing hyperprogression as a response to cancer treatment with immune checkpoint inhibitors, say researchers.
Of 182 patients with a range of solid tumors who were enrolled in early-phase immunotherapy trials at a Canadian institution between 2012 and 2016, 7% had hyperprogressive disease, defined as progression according to RECIST criteria at the first on-treatment scan and a twofold or greater increase in tumor growth rate from the pre- to post-immunotherapy scan.
Hyperprogressive disease was significantly more common among women than men, with 83% of the instances of hyperprogression occurring in women, according to the report published in Cancer.
“Although this finding requires further validation in a larger cohort, it is intriguing in light of evidence for sex-specific effects of immunotherapy,” as shown in a meta-analysis of 20 randomized controlled trials published last year, comment the researchers.
Adding to the big picture: An updated meta-analysis showed no difference in efficacy of cancer immunotherapy by sex – click through to read the report.
No other factor investigated was found to significantly predict hyperprogressive disease. These included age, tumor volume or type, ECOG performance status (PS), Royal Marsden Hospital prognostic score, prior lines of immunotherapy, receipt of monotherapy or combination therapy, and toxicity.
The median age of the study participants was 60 years and the majority (54%) were women. Sixty-eight percent of the patients had an ECOG PS score of 1, while the remaining 32% had a score of 0. Tumors of the head and neck were the most common (18%), followed by gynecologic (16%), lung (15%), gastrointestinal (15%), and genitourinary (12%) cancer. The participants predominantly (80%) received monotherapy with immune checkpoint inhibitors, most frequently anti-PD-1 or anti-PD-L1 agents (70%).
Hyperprogression was associated with a significantly shorter median progression-free survival time, at 1.6 months versus 2.8 months for the group that did not have hyperprogressive disease (hazard ratio=3.7).
Although overall survival was numerically shorter for participants with versus without hyperprogression, at a median of 5.9 and 14.3 months, respectively, the between-group difference did not reach statistical significance, which the researchers suggest could be due to the small sample size.
“The lack of agreement about the definition of [hyperprogressive disease] in the literature makes direct comparisons of data challenging, although multiple studies do provide support for the concept of hyperprogression during immunotherapy,” say Philippe Bedard and colleagues, from the Princess Margaret Cancer Centre in Toronto, Ontario, Canada.
And they hope that the use of novel tools, such as circulating tumor DNA analysis and a recently developed radiomic CD8-cell signature, may help to assess and predict response to immunotherapy.
“These technologies may distinguish between hyperprogression and pseudoprogression in patients with an accelerated [tumor growth rate] early in their course of immunotherapy treatment,” the team concludes.
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