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Biomarker May Help Distinguish Between Pseudoprogression and True Disease Progression in Metastatic Melanoma

By: Cordi Craig
Posted: Thursday, April 26, 2018

A study led by Jenny H. Lee, MBBS, of Macquarie University, in Sydney, Australia, found that measuring circulating tumor DNA (ctDNA) may help distinguish between pseudoprogression and true progression in patients with metastatic melanoma who receive anti–PD-1 antibody treatment. The results, published in JAMA Oncology, suggest that ctDNA profiles could be a “powerful” tool for predicting long-term responses and survival.

Over 2 years, a cohort of 125 patients receiving PD-1 antibody treatment alone or in combination with ipilimumab were assessed for circulating BRAF and NRAS mutations.  Investigators evaluated ctDNA in plasma samples at baseline and during the first 12 weeks of treatment. A favorable profile consisted of undetectable ctDNA at baseline or detectable ctDNA at baseline with a subsequent 10-fold decrease. An unfavorable profile consisted of detectable ctDNA at baseline that remained stable or increased. Profiles were associated with response and prognosis.

Progressive disease occurred in 29 of 125 patients (23%). In this subgroup, 9 patients (31%) had pseudoprogression and 20 (69%) had true progression. All of the patients who showed pseudoprogression had a favorable ctDNA profile. Unfavorable profiles were observed in 18 of the 20 patients with true progression. Patients with a favorable ctDNA profile had a 1-year survival rate of 82% versus 39% in patients with an unfavorable ctDNA profile. The sensitivity and specificity of ctDNA for predicting pseudoprogression were 90% and 100%, respectively.



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