Experts Make the Case for Buprenorphine Use in Cancer-Related Pain Management

Buprenorphine may be an effective pain management strategy for various populations of patients with cancer, according to palliative care experts Mary Lynn McPherson, PharmD, BCPS, FAAHPM; and Amy A. Case, MD, FAAHPM.¹ The agent’s unique pharmacology, and clinical utility and safety data, make it a preferable choice over traditionally used opioids.

Mary Lynn McPherson, PharmD, BCPS, FAAHPM

McPherson, who is a professor at the University of Maryland, Baltimore, and executive director of the Advanced Post-Graduate Education in Palliative Care, Graduate Studies in Palliative Care, and Online Graduate Studies in Palliative Care programs, and Case, who is the chair of Supportive and Palliative Care at Roswell Park Comprehensive Cancer Center, recently participated in an invited speaker session titled “Why Consider Buprenorphine for Cancer-Related Pain?” at the 2022 Supportive Care in Cancer Annual Meeting.

Unique Pharmacology

The oral bioavailability associated with buprenorphine is low. Therefore, it is not swallowed as a pill. It is taken sublingually or through a patch that should be rotated to a different site and then returned to the original site every 21 days according to the package insert.

Amy A. Case, MD, FAAHPM

“It is a really good option [for] those with who cannot swallow,” Case said.

“Generally, we use it on the upper body and areas where there is not a large amount of subcutaneous fats,” she explained.

Moreover, buprenorphine functions differently compared with traditional μ-opioid receptor agonists, explained McPherson. The agent binds to μ, δ, κ, and opioid receptor-like 1 (ORL1). It has a very high binding affinity to the μ receptor, as well as with the δ and κ receptors, but a lower binding affinity for ORL1. However, it is a partial μ agonist and not a full μ-opioid agonist.

As a partial agonist, buprenorphine has less μ-receptor signaling, which may result in fewer opioid-related adverse events. However, this does not mean buprenorphine is not an effective analgesic. It has a higher binding affinity compared with most full μ-opioid agonists, suggesting that it is a very effective pain management option.²

Several studies with large numbers of patients with cancer have documented that pain management with buprenorphine is effective, Case said. For example, in one study, 85% of patients reported their pain control to be “good” or “very good” and 48% of patients reported improvement in sleep quality.¹

“A lot of our patients in palliative care or supportive care in oncology have issues with sleep,” Case explained. “[Buprenorphine,] has been shown to be equivalent to other traditional used opioids [in managing this symptom].”

It has also demonstrated a benefit for neuropathic pain and successfully blocks secondary hyperalgesia from central sensitization. Its analgesic benefit is thought to be comparable to morphine, hydromorphone, oxycodone, fentanyl, and methadone.

Furthermore, its high potency and slow dissociation rate allows for effective treatment at lower doses, Lin added.

Clinical Safety

Buprenorphine has less beta-arrestin activity than traditional opioids once it binds¹, Case explained. Beta-arrestin is linked with negative responses such as endocytosis, physical dependency, respiratory depression, and constipation.

In addition, buprenorphine is associated with less cognitive dysfunction than with other opioids, making it a viable choice for elderly patients. “There is less impairment [compared] with equal doses of morphine,” Case said. “Several studies have shown improved sleep, pain, quality of life in the elderly [who receive buprenorphine].”¹

Notably, the pharmacokinetics are not altered with age, so there are no required dose reductions for elderly patient populations, and it is the only opioid that is not associated with risk of fracture, although Case noted that there is insufficient literature on this risk.

Across all populations, buprenorphine represents a potentially safer alternative for patients at risk for dependency disorders, since it does not induce euphoria, and is therefore associated with reduce abuse liability. It is safe in patients with renal and liver impairment, although for patients with severe liver impairment, a 50% dose reduction is advised because the drug is metabolized by the liver. It is also associated with a reduced risk of respiratory depression.

Finally, because the drug is a κ antagonist, patients may have less anxiety, lytic effects, depression, or suicidal tendencies compared with traditional opioids.¹ This may also limit the addictive potential.

“[There are] some papers out there showing that up buprenorphine is actually used as a treatment for depression,” Case said.

A Note on Accessibility

Case acknowledged that some providers may find it difficult to get insurance companies to cover buprenorphine. However, in her experience, most companies will if presented with data on the drugs’ efficacy.

In 2019, the US Department of Health and Human Services published their Pain Management Best Practices Document. The document lists the following recommendations:³

Recommendation 4a: Make buprenorphine treatment for chronic pain available for specific groups of patients and include buprenorphine in third-party payer and hospital formularies.

Recommendation 4b: Encourage CMS and private payers to provide coverage and reimbursement for buprenorphine treatment, both for opioid use disorder and for chronic pain. Encourage primary use of buprenorphine rather than use only after failure of standard μ agonist opioids such as hydrocodone or fentanyl, if clinically indicated.

Recommendation 4c: Encourage clinical trials using buprenorphine for chronic pain to better understand indication, usage and dosage.

“When the insurance companies give me a hard time about, I send [the recommendations] to them and clog up their fax machines and then they cover it,” Case concluded.

Reference

1. McPherson ML, Case AA. Why consider buprenorphine for cancer-related pain? Presented at: 2022 Supportive Care in Cancer Annual Meeting; June 23-25, 2022; Toronto, Ontario. https://bit.ly/3ykukgm
2. Gudin J, Fudin J. A narrative pharmacological review of buprenorphine: a unique opioid for the treatment of chronic pain. Pain Ther. 2020;9(1):41-54. doi:10.1007/s40122-019-00143-6
3. Pain management best practices best practices inter-agency task force report, updated gaps, inconsistencies, and recommendations. US Department of Health and Human Services. Accessed June 24, 2022. https://bit.ly/2PWM5u3