Background: About 30% of cancer patients presenting with pain have symptomatic improvement using conventional strategies within one month. PGx may help personalize opioid selection and improve cancer pain management.

Methods: This is a pragmatic pilot trial investigating the feasibility and application of PGx testing to improve pain management in adults with uncontrolled cancer pain referred to an oncology PM clinic. PM providers assessed patients using Edmonton Symptom Assessment Scale at baseline and opioid therapy was initiated or modified. A buccal swab was obtained for genotyping single nucleotide polymorphisms in: COMT, CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP3A4, CYP3A5, and OPRM1. The first assessment occurred within one week of baseline and a second within another week if intervention was required. PGx results were available before the first assessment and utilized, if applicable, throughout the one-month study period. Pain improvement rate (≥ 2-point reduction on a 0-10 scale) from baseline to final visit, was compared to historical control data by a one-sided exact binomial test of proportions.

Results: Of 75 undergoing PGx testing, 52 were evaluable for the primary endpoint (54% female, 81% white, 17% black, median age 63, 75% stage 3 or 4 disease, median personalized pain goal 3 [0-6]). 56% had pain improvement compared to 30% in historical controls (p < 0.001). At final assessment, 35% met their personalized pain goal. Of 26 (50%) requiring opioid adjustments, 18 (69%) had an actionable genotype with a 61% pain improvement rate. The two most common genes for opioid adjustment were CYP2D6 (16/18; 89%) and COMT (8/18; 44%). The most common PGx-guided modification involved switching from a CYP2D6-metabolized drug (hydrocodone, oxycodone, tramadol) to a non-CYP2D6-metabolized drug (fentanyl, hydromorphone, methadone, morphine).

Conclusions: PGx implementation in an oncology PM clinic was feasible and improved pain management. Half of those requiring opioid adjustments had an actionable genotype, with the largest impact from CYP2D6 polymorphisms. Future studies should focus on preemptive PGx testing to guide initial drug selection and confirm clinical utility in a randomized trial.