ctDNA flags up pseudoprogression during melanoma treatment
medwireNews: Circulating tumor (ct)DNA can differentiate pseudoprogression from true disease progression in patients with metastatic melanoma undergoing immunotherapy, a study suggests.
The Australian researchers believe measurements of the marker could be used to aid early treatment decisions in patients receiving anti-programmed cell death protein 1 (PD-1) antibodies.
Specifically, they found ctDNA reductions within 12 weeks of anti-PD-1 inhibitor treatment identified pseudoprogression and represented a liquid molecular biomarker profile for prognosis.
“Results of this blood test performed at regular intervals during systemic treatment reflect tumor biology and have potential as a powerful biomarker to predict long-term response and survival,” the team maintains in JAMA Oncology.
Matteo Carlino (Westmead Hospital, Sydney, New South Wales) and colleagues studied 125 patients with BRAF or NRAS mutation-positive stage IV melanoma receiving the anti-PD-1 antibodies pembrolizumab or nivolumab alone or in combination with ipilimumab.
Plasma samples of ctDNA were assessed at baseline and taken for analysis prospectively over the first 12 weeks of treatment, with progressive disease developing in 23.2% of patients according to RECIST guidelines.
But among these 29 patients, nine (31%) were considered to have pseudoprogression due to radiologic progression not being confirmed as progressive disease at the next radiologic assessment. The remaining 20 patients showed true progression, defined as new or growing lesions detectable within 12 weeks of treatment initiation.
All patients with confirmed pseudoprogression had a favorable ctDNA profile, defined as undetectable ctDNA at baseline and during treatment or detectable ctDNA at baseline that became undetectable or decreased at least 10-fold within 12 weeks of treatment. At a median follow-up of 110 weeks, seven (78%) of these nine patients were alive.
By contrast, all but two of the 20 patients with true progression had an unfavorable ctDNA profile, defined as detectable ctDNA at baseline that remained stable or increased.
The ctDNA profile had 90% sensitivity and 100% specificity for predicting pseudoprogression, the team reports. But these profiles were also associated with overall survival (OS) in patients with true progressive disease, they note, with 1-year OS rates of 82% for patients with a favorable ctDNA profile versus 39% for those with unfavorable ctDNA (hazard ratio of 4.8).
The researchers conclude: “Circulating tumor DNA 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.”
By Anita Chakraverty
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