3298 - Early identification of treatment effect by methylated circulating tumor DNA in metastatic colorectal cancer

Background

Early identification of treatment effect is wanted in several settings, including management of metastatic colorectal cancer (mCRC). A potential universal marker is circulating tumour DNA (ctDNA). Our prospective study explored the association between progression free survival (PFS) and overall survival (OS), and early change of ctDNA after one cycle of chemotherapy in patients with mCRC.

Methods

The study included mCRC patients receiving standard first line combination chemotherapy with 5-FU, oxaliplatin, and bevacizumab. Hypermethylated neuropeptide Y (NPY) ctDNA (meth-ctDNA) served as a marker analyzed by droplet digital PCR. The meth-ctDNA level was analyzed in plasma before treatment start and again before cycle two. The patients were divided into two groups according to the dynamics of meth-ctDNA. Group 1 included patients with zero or values of meth-ctDNA decreasing to a level including zero in the 95% confidence interval. Group 2 included all other patients (stable, increasing, or slightly decreasing values). The two groups were compared as to PFS and OS.

Results

The study included 107 patients with both of the two blood samples analyzed. The PFS in the two groups was significantly different with a median of 9.5 and 7.4 months, respectively (p = 0.002). This translated into a 12- month difference in OS at a median of 25.4 and 13.5 months, respectively (p = 0.0001).

Conclusions

Early therapeutic reconsideration is of utmost importance. The level of meth-ctDNA after one cycle of chemotherapy in the first line setting seems to divide the patients into two groups with minimal and maximal benefit of treatment. The clinical utility should be confirmed in randomized clinical trials.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

L.H. Jensen: Research grant / Funding (institution): MSD; Research grant / Funding (institution): BMS; Research grant / Funding (institution): 2cureX (research). All other authors have declared no conflicts of interest.