CAP TODAY Pathology/Laboratory Medicine/Laboratory Management
MDxHealth announced data showing that methylation of the DCR1 gene may help guide oncologists in selecting metastatic colorectal cancer patients to receive irinotecan-based therapy. The data, presented at this year’s ASCO meeting, showed that CRC patients with methylated DCR1 did not benefit from the addition of irinotecan to capecitabine therapy.
Identification of DCR1 as a novel hypermethylated gene associated with a lack of benefit in adding irinotecan to capecitabine when treating metastatic colorectal cancer was performed in the Department of Pathology at the VU University Medical Center, Amsterdam.
The presence of DNA methylation for a panel of 22 genes was assessed on the primary tumors of 185 patients with metastatic CRC treated with firstline capecitabine (CAP, n=90) or a combination of capecitabine and irinotecan (CAPIRI, n=95) in the phase-three CAIRO trial. The methylation status of each gene was correlated to progression-free survival by treatment regimen. Genes for which methylation status was associated with response to irinotecan were validated in 166 patients treated with firstline CAP (n=78) or CAPIRI (n=88). In CAPIRI-treated patients, DCR1 methylation was correlated to a shorter PFS compared with patients with unmethylated DCR1 (hazard ratio [HR]=0.4, P=0.0009). In patients with methylated DCR1, PFS did not improve with CAPIRI treatment, compared with treatment with CAP (discovery set: HR=0.8, P=0.4; validation set: HR=1.1, P=0.6), in contrast to patients with unmethylated DCR1 (discovery set: HR=2.5, P=0.00004; validation set: HR=1.7, P=0.004).
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