A recent study conducted in a palliative care setting investigated the use of a genetic biomarker with possible relevance to opioid response. The study investigators determined that this genotype on its own is not recommended for deciding between morphine and oxycodone for providing pain relief. The study findings were published in the journal The Oncologist.

The COMT gene, which encodes the catechol-O-methyltransferase (COMT) enzyme, appears as a variant in some people called the rs4680-GG variant. “As the COMT enzyme metabolizes catecholamines, a high COMT enzyme activity could result in reduced activation of dopaminergic neurotransmission,” the study investigators explained in their report.

Patients show variation in the requirement for morphine to alleviate pain, beyond the level of pain intensity, the investigators explained. COMT has been considered a possible contributor to interpatient variation, but research has been unclear on this point. For this reason, the investigators conducted a trial to examine the use of the COMT rs4680-GG genotype as a biomarker for determining opioid choice.

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In this multicenter, randomized, controlled, open-label trial based in Japan, patients with cancer-related pain were classified by whether they had the rs4680-GG (GG) genotype or a non-rs4680-GG (non-GG) genotype. They were then randomly assigned 1:1 to receive either morphine or oxycodone for pain management. Minimum standard doses of either agent could be repeatedly administered until pain-reduction goals were achieved (a reduction in pain of 33% or greater from baseline and a score of 3 or less on a numerical rating scale). The primary study endpoint was the proportion of patients with the rs4680-GG genotype who required high-dose opioids on day 0.

Of the 59 patients in the GG genotype group, 29 were assigned to receive morphine and 30 to receive oxycodone. Of the 80 patients in the non-GG genotype group, 41 were assigned to receive morphine and 39 to receive oxycodone.

Overall, among the patients in the GG genotype group, high-dose opioids were required in 48.3% of those receiving morphine and 20.0% of those receiving oxycodone (P =.029). Among patients in the non-GG genotype group, high-dose opioids were required in 41.5% and 23.1% of those receiving morphine and oxycodone, respectively (P =.098).

For patients with the rs4680-GG genotype, high-dose opioids were needed at a significantly higher rate with morphine than with oxycodone. However, the trend toward this pattern also occurred among patients with a non-rs4680-GG genotype, the investigators noted. Although this pattern lacked statistical significance in patients with a non-rs4680-GG genotype, the investigators considered the trend suggestive of factor(s) beyond the rs4680 genotype in explaining these observations.

“As several factors other than genetics, such as etiology and environmental factors, could also affect the opioid response, the impact of genetic differences may vary with respect to their relationship with these factors,” the study investigators wrote in their report.

Disclosures: Some authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Matsuoka H, Tsurutani J, Chiba Y, et al. Morphine versus oxycodone for cancer pain using a catechol-O-methyltransferase genotype biomarker: a multicenter, randomized, open-label, phase III clinical trial (RELIEF study). Oncologist. Published online November 25, 2022. doi:10.1093/oncolo/oyac233