The clinical outcomes of melanoma patients who may benefit from combination immunotherapy can be predicted with circulating tumor DNA (ctDNA) in the first-line immune checkpoint inhibitor (ICI) treatment setting but not in the second-line setting, according to a recent study in Clinical Cancer Research (2020. doi:10.1158/1078-0432.CCR-20-2251).
“Immunotherapy has become an increasingly common treatment for patients with melanoma, often as the second-line treatment after disease progression on BRAF inhibitors,” explained Elin Gray, PhD, School of Medical and Health Sciences, Edith Cowan University (Perth, Australia). “There is a lot of interest in identifying biomarkers that reliably indicate how patients will respond to this treatment.”
Researchers evaluated the predictive value between baseline ctDNA levels from 125 samples collected from 110 patients to inform therapeutic outcomes in patients with metastatic melanoma comparative to type and line of treatment. The ctDNA was collected prior to commencing treatment with ICIs, as first- or second-line regiments, or prior to commencing first-line BRAF/MEK inhibitor therapy. Thirty-two patients were treated with ICIs as first-line regimens, and 27 were treated with second-line regimens. Sixty-six patients received first-line treatment with targeted therapy.
In patients treated with first-line ICIs, but not second-line, low baseline ctDNA levels (<20 copies per milliliter) predicted longer progression-free survival (PFS) prior to starting therapy. The results were validated in a separate cohort of 128 patients with melanoma recruited at other institutions across Australia. In patients pretreated with BRAF/MEK inhibitors, ctDNA was not predictive of PFS. Patients with high baseline ctDNA levels had reduced PFS and overall survival.
“Our results indicate that it is necessary to carefully consider context when implementing biomarkers,” said Dr Gray. “ctDNA is often heralded as a good prognostic biomarker, but we found that this is not the case for patients receiving immune checkpoint inhibitors in the second-line setting.
“We need more of these kinds of studies evaluating the accuracy of ctDNA in various disease contexts, particularly now that liquid biopsy and ctDNA are being increasingly incorporated into the clinic.”—Lisa Kuhns