Blood Test Predicts Patient Response to Chemotherapy

Early changes in circulating tumor DNA (ctDNA) level may provide early response prediction, but the impact of tumor heterogeneity is unknown.

A blood test for cancer DNA could predict if a woman is responding to the new breast cancer drug palbociclib, months earlier than current tests and this test could detect in two to three weeks whether the drug is working.

A team of scientists working with The Institute of Cancer Research (London, UK) enrolled 521 women, randomizing in a 2:1 ratio to receive palbociclib plus fulvestrant or fulvestrant plus placebo. The ctDNA was conducted on plasma samples collected prospectively for ctDNA analysis. The primary aim of this study was to assess ctDNA mutations and dynamics as a biomarker of progression-free survival, and to compare the dynamics of Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Alpha (PIK3CA) and Estrogen Receptor 1 (ESR1) mutations.

The team estimated the DNA concentration in each sample by assessment with a TaqMan Copy Number Reference Assay against Ribonuclease P RNA Component H1 (RPPH1), the gene-encoding RNAseP. Using the AutoDG automated droplet generator, samples were partitioned into approximately 20,000 micelles in emulsion and polymerase chain reactions (PCR) performed. The wells were analyzed on a Bio-Rad QX200 instrument for FAM and VIC signal in each droplet.

The scientists reported that in the 73 women who had the PIK3CA mutation and were given blood tests before and after starting palbociclib treatment. They had a small decrease in PIK3CA circulating DNA at 15 days had a median progression-free survival (the length of time the patient survived and the cancer did not get worse) of only 4.1 months, compared with women with a large decrease in PIK3CA, who had a median progression-free survival of 11.2 months. The results suggest that early ctDNA dynamics may provide a robust biomarker for cyclin D–dependent kinase (CDK)4/6 inhibitors, with early ctDNA dynamics demonstrating divergent response of tumor sub clones to treatment.

Nathan Richardson, PhD, Head of Molecular and Cellular Medicine at the Medical Research Council, said, “It is exciting to see that using advances in diagnostic techniques, such as genetic tests for circulating tumor DNA, we may be able to more accurately define groups of patients and help us deliver the right treatment to the right patient sooner. This study provides early evidence that might help us understand sooner when a drug is successfully treating breast cancer, and if not, it can be discontinued and better approaches pursued.” The study was published on March 1, 2018, in the journal Nature Communications.

Related Links:
The Institute of Cancer Research