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A study published in Nature Cancer showed that blood levels of DNA from solid tumours (circulating tumour DNA or ctDNA) were associated with the prognosis of cancer patients with different types of tumours who had been treated with pembrolizumab.
The study included 94 patients with various solid tumours who were treated with pembrolizumab. ctDNA levels varied between tumour types and tumour size was not related to baseline ctDNA levels. Patients with breast cancer had the highest levels of ctDNA, while patients with melanoma had the lowest levels. Prolonged overall survival was significantly associated with low baseline ctDNA levels as was progression-free survival. Patients with low baseline levels of ctDNA also had higher clinical benefit rate and trended toward an improved response rate.
Changes in ctDNA levels during treatment with pembrolizumab resulted in an overall survival and objective response rate benefit. A reduction in ctDNA levels from baseline was also associated with prolonged overall survival and progression-free survival.
Throughout treatment with pembrolizumab, any increase above ctDNA baseline levels was associated with rapid disease progression and poor survival. ctDNA levels below baseline were associated with mixed responses. “If, however, ctDNA cleared during treatment, superior clinical outcomes were observed,” the authors wrote. This occurred in 12 patients who demonstrated objective responses and median overall survival of 25.4 months.
The authors concluded that “the findings from this prospective study suggest broad clinical utility for ctDNA-based surveillance in immune checkpoint blockade-treated patients.”
