In 2015, an unprecedented phenomenon occurred in the United States: according to the World Bank Group, the nation’s average life expectancy fell from 78.8 years in 2014 to 78.7 years in 2015, then to 78.5 years in 2017. The last time our life expectancy registered a similar decline was in the years 1915 to 1918, as a result of WWI and the influenza pandemic. This time, the decline in life expectancy was due, in part, to waves of overdose deaths related to the “opioid epidemic,” which began in the 1990s.
In response to public outcry, federal and state regulators enacted a series of tough laws and regulations that substantially decreased opioid prescribing across the nation. However, the oncology community voiced concern that well-meaning drug legislation to curtail overprescribing could also hamper the delivery of pain management to our most vulnerable citizens: patients with cancer.
In its policy statement, ASCO stressed: “Patients with cancer represent a special population that should be largely exempt from regulations intended to restrict access or limit doses, in recognition of the unique nature of the disease, its treatment, and potentially lifelong sequelae.”
Undertreated Cancer Pain
Although most of the legislative efforts to curtail overprescribing recognized the special pain management needs in oncology, little research has been directed toward understanding the trends in opioid access among patients with end-stage cancer. A recent study published in the Journal of Clinical Oncology found that opioid use among patients dying of cancer has substantially declined from 2007 to 2017, with rising pain-related emergency department visits, which indicates that, on certain levels, cancer pain management may be worsening.1
Andrea C. Enzinger, MD
One of the study’s lead authors, Andrea C. Enzinger, MD, told The ASCO Post: “My colleagues and I have been discussing the topic of undertreatment of cancer pain within the context of the opioid crisis for a number of years. For obvious reasons, over the past decade, the bulk of the attention and research in the policy world has focused on the issue of opioid abuse, addiction, and fatal overdose. However, over that same decade, we have also seen a growing trend in the underprescribing of opioids for our patients with cancer.”
She continued: “To date, there hasn’t been a rigorous study on how the laws and public attitude have affected prescribing habits among oncologists. But if there is one population that should be protected from these added regulatory burdens that pose challenges to opioid access, it is our patients dying of cancer.”
According to Dr. Enzinger, she and her coauthors realized that tough prescribing laws enacted to quell the shocking numbers of opioid overdose deaths had also exacerbated the undertreatment of pain among patients with cancer. They looked at 270,632 Medicare fee-for-service decedents with poor-prognosis cancers, using part D data to examine trends from 2007 to 2017 in opioid prescription fills and opioid potency near the end of life, which was defined as the 30 days before death or hospice enrollment.
“What we found was staggering,” said Dr. Enzinger. “Opioid prescribing to patients with cancer in their last month of life dropped by nearly 40%. We teased it out by different classes of medications and found the biggest reduction in prescribing was for long-acting opioids. Within that context, it’s important to note that in the moderate-to-severe cancer pain setting, World Health Organization guidelines recommend around-the-clock opioid analgesia in order to keep ahead of the pain curve and prevent a yo-yo effect, which ultimately causes undue suffering. The way to do this is by using a long-acting opioid, which remains in the system for up to 12 hours, so we don’t have to be constantly chasing the tail of the pain.”
Alexi A. Wright, MD, MPH
Study senior author Alexi A. Wright, MD, MPH, commented: “Leading up to the implementation of new drug prescribing laws and the [Centers for Disease Control and Prevention] guidelines, there had been concern about the effect these initiatives would have on pain management. Although the laws and legislation had specifically stipulated that patients with cancer were exempt from directives curbing opioid prescribing, small surveys indicated that these patients were indeed having access issues, and there was a growing reluctance among oncologists to go through all the extra burdens in order to prescribe adequate amounts of opioids for their patients. That’s why we did this population-based study, which I believe is the first of its kind in this area.”
Dr. Wright continued: “Another important finding, although not necessarily causal, was that the pain-related emergency department visits went up markedly in the cohort of dying patients with cancer, which is the last thing you want to see as a clinician. Instead of being in the comfort of their home, with their pain being managed, these patients are spending time during the last days of their lives sitting in a crowded emergency room waiting for pain meds. That’s an unintended consequence of the backlash created by very tough laws enacted to restrict overprescribing—something I’m sure nobody writing the laws expected.”
In an Editorial published in the Journal of the National Cancer Institute,2 Drs. Enzinger and Wright commented: “Writing an opioid prescription has become a complex process that involves signing controlled substance agreements, checking prescription drug–monitoring programs, responding to phone queries from conscientious pharmacists, filing prior authorization paperwork, and even rewriting prescriptions to comply with seemingly arbitrary and sometimes conflicting rules set by states, insurers, and pharmacies.” This onerous process that disincentivizes oncologists from prescribing opioids has been documented; however, public perception surrounding issues of stigma and addiction, which also discourage patients from taking adequate pain medications, are more difficult to quantify.
To that end, Dr. Enzinger was part of a study published in Cancer looking at pain management in the context of the opioid epidemic.3 “We interviewed 26 patients with advanced cancer who were prescribed opioids to manage their pain and asked them about their experience. Without prompting, the number one theme in all of the interviews was the opioid epidemic and the fear of becoming addicted. It’s important to mention that the media has covered the tragedy of opioid addiction extensively; yet little attention has been paid to necessary uses of opioids, such as in patients with cancer, which adds to much of the public now viewing these valuable drugs as inherently dangerous and their use immoral,” said Dr. Enzinger.
Dr. Enzinger noted that several patients in the study also described receiving pushback from pharmacy staff in the form of questions to corroborate the legitimacy of their opioid requirements or requests to speak directly to the prescriber. These lines of questioning were uniformly perceived as judgmental and publicly humiliating by the patients. This extra scrutiny and the additional logistical barriers served to reinforce participants’ moral distress, concerns about addiction, and even anger toward people who abused opioids.
“The bottom line is that the messaging about opioids and proper cancer pain control is getting conflated with the human devastation and stigmatization of the opioid epidemic. We cannot say whether our findings are generalizable to other populations, but we concluded that promoting more awareness and proactive communication regarding the opioid stigma is an important strategy to better supporting patients coping with advanced cancer pain,” said Dr. Wright.
DISCLOSURE: Dr. Enzinger has an immediate family member who has been a consultant or advisor to Five Prime Therapeutics, Merck, Astellas Pharma, Lilly, Loxo, Taiho Pharmaceutical, Daiichi Sankyo, AstraZeneca, Zymeworks, Takeda, Istari Oncology, Ono Pharmaceutical, Xencor, ALX Oncology, and Bristol Myers Squibb. Dr. Wright has been a consultant or advisor to GlaxoSmithKline and has received research funding from NCCN/AstraZeneca.
1. Enzinger AC, Ghosh K, Keating NL, et al: US trends in opioid access among patients with poor prognosis cancer near the end-of-life. J Clin Oncol 39:2948-2958, 2021.
2. Enzinger AC, Wright AA: Reduced opioid prescribing by oncologists: Progress made, or ground lost? J Natl Cancer Inst 113:225-226, 2021.
3. Azizoddin DR, Knoerl R, Adam R, et al: Cancer pain self-management in the context of a national opioid epidemic: Experiences of patients with advanced cancer using opioids. Cancer 127:3239-3245, 2021.