medwireNews: Circulating tumour (ct)DNA profiles can identify pseudoprogression in patients receiving immunotherapy with anti-programmed cell death protein 1 (PD-1) agents for metastatic melanoma, report Australian researchers.
They explain that “[e]arly recognition of this unique response pattern has important implications for patient management”, by potentially preventing “premature termination of potentially effective treatment and [influencing] the selection and administration of optimal sequential therapy in a time-sensitive manner.”
Matteo Carlino (Westmead Hospital, Sydney, New South Wales) and co-researchers believe that ctDNA has the potential to serve as “a powerful biomarker” in this setting.
Among 125 patients with BRAF or NRAS mutation-positive stage IV melanoma who received pembrolizumab or nivolumab, either alone or alongside ipilimumab, between 2014 and 2016, 29 were classed as having progressive disease as per the RECIST criteria at the 12-week mark after initiation of therapy.
But for nine patients, this initial increase in tumour burden was not confirmed at the subsequent radiological assessment, and therefore they were considered to have experienced pseudoprogression.
The study authors report in JAMA Oncology that all patients with pseudoprogression had a favourable ctDNA profile, defined as undetectable levels at baseline that remained undetectable during treatment or detectable levels that either became undetectable or decreased by at least 10-fold. By contrast, only two of the 20 participants with true progression had a favourable ctDNA profile.
The ctDNA profile could discriminate pseudoprogression from true progression with a sensitivity of 90% and a specificity of 100%.
These profiles of ctDNA were also associated with overall survival (OS). Specifically, among patients who progressed, those with a favourable ctDNA profile had significantly better OS than those with an unfavourable profile, with a hazard ratio of 4.8, and corresponding 1-year rates of 82% and 39%.
Matteo Carlino et al say that ctDNA “has the potential to be an early treatment decision-making tool, and novel clinical trial designs could use ctDNA profiles to identify patients for treatment escalation.”
They continue: “The use of ctDNA to identify these unique response measures should be explored for additional diseases beyond melanoma.”
Lee JH, Long GV, Menzies AM, et al. Association between circulating tumor DNA and pseudoprogression in patients with metastatic melanoma treated with anti–programmed cell death 1 antibodies. JAMA Oncol; Advance online publication 8 February 2018. doi: 10.1001/jamaoncol.2017.5332
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