Can circulating tumor DNA predict patient response to targeted therapy?

The aim of this study was to evaluate if cell-free circulating tumor DNA (ctDNA) in the blood could predict a patient's response to targeted therapy. The study found that measuring ctDNA could predict how a patient would respond to therapy.

Melanoma is a form of skin cancer. Treatment for early-stage melanoma includes surgery to remove the tumor. For more advanced melanoma, patients can be treated with targeted therapy. Tumor cells develop specific genetic changes to help them survive and grow. Targeted therapy stops these genetic changes from working. The tumor cells rely on these genetic changes so heavily that when they no longer work, the tumor cells die. Targeted therapies often used in melanoma are dabrafenib (Tafinlar) and trametinib (Mekinist).

A biomarker is something that can be measured from a patient that gives information about the tumor. If the biomarker can be detected in the blood, measuring this biomarker is less invasive for the patient. Currently, there are no biomarkers for melanoma.

ctDNA is a potential biomarker for many cancers. ctDNA is released by a dying tumor cell and enters the blood. It is unknown if levels of ctDNA can predict how a patient with melanoma will respond to targeted therapy.

This study evaluated data from two clinical trials. In trial 1, patients were treated with dabrafenib plus trametinib or dabrafenib plus a placebo. In trial 2, patients were treated with dabrafenib plus trametinib. Blood samples were taken from patients before and during treatment.

In trial 1, ctDNA was detected in 93% of patients at the beginning of trial 1. 60% of these patients still had ctDNA after 4 weeks of treatment. Patients who had high ctDNA at the start of the trial were 13% more likely to have a worse outcome. Patients who had lower levels of ctDNA (fewer than 64 copies/mL) 4 weeks after treatment were 2.23 times more likely to have a better survival outcome compared to a higher level of ctDNA.

In trial 2, ctDNA was detected in 89% of patients at the start of trial 2. Patients with lower ctDNA were 21% more likely to have a better survival outcome.

The study concluded that ctDNA measurements could predict how well a patient would respond to targeted therapy.

Only one of the trials evaluated in this study was randomized. The sample size in the second study was small. The study was designed and funded by Novartis who manufacture dabrafenib and trametinib. Long-term ctDNA measurements were not available for most patients.