Keith Loria is a contributing writer to Medical Economics.

Keith Loria

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There’s a cancer problem in the U.S., say many experts, and dazzling new treatments and brilliant scientific advances are not going to solve it.

The problem is cancer’s disproportionate effect on Black people in the United States, who have the highest death rate and shortest survival periods of any racial or ethnic group in the country. For many of the most common cancers (lung, breast, colon, prostate), the incidence rate among Black people is lower than the rate among white non-Hispanic people, yet the death rate among Black people is higher.

Most of these disparities are nothing new and have long been recognized. What has changed is the thinking (and research) into their causes. For many years, the tip of the cancer research spear was directed at genetic and biological explanations. Researchers and policymakers as well as oncologists are now focusing on societal factors and structural racism as the root cause of much of the disparity.

Anita Johnson, M.D., FACS, chief of surgery and leader of the Women’s Cancer Center at Cancer Treatment Centers of America in Atlanta, says the challenges to accessing cancer care for minorities are multifactorial. Many can be traced to the social determinants of health (SDOH) that can put access to quality care, insurance, oncologists and clinical trial enrollment out of reach.

“Other challenges, such as access to healthy food options and environmental circumstances that expose individuals to carcinogens, also play a role,” continues Johnson, who also mentions the cultural barriers created by the lack of minorities in the health care professions. For example, recent research has shown that only 3% of oncologists in the U.S. are African American.

Christina Chapman, M.D., an assistant professor of radiation oncology at the University of Michigan Medical School, says the vast majority of the cancer-related issues that minority populations face are due to past or ongoing rules, norms, or laws that maintain societal inequity.

“Downstream problems like a lack of access to high-quality screening and treatment, or to clinical trials, are heavily rooted in societal inequity,” she says. “In the long term, social reform is needed to address inequity in income, wealth and health insurance access. In the short to medium term, health systems and cancer care providers need to recognize how inequity affects their patient populations and use existing resources that do help ensure that everyone has access to current therapies instead of solely focusing on new innovations that will not be accessible to many in the population.”

Most cancers are caused by a complicated web of factors. The causal pathway gets even more complex with outcomes such as the five-year survival rate and death because of the many issues that influence access and the use of health care. All this complexity comes under the heading of SDOH, which loom large in the current understanding of the causes of cancer disparities.

“For example,” says Johnson, “regardless of education level, Black women in the U.S. are known to have a higher rate of unemployment than White women. Being gainfully employed frequently provides individuals with benefits like health insurance and paid time off. These are important contributing factors to access screening, which can lead to earlier diagnoses of cancer and subsequently better outcomes, as well as the ability to seek and maintain cancer treatment.”

The incidence of breast cancer among White and Black women is similar, but Black women are 40% more likely to die from the disease. Higher rates of obesity and other health problems may be a factor (they may have upstream SDOH causes). Black women are also more likely to be diagnosed with aggressive types of the disease, such as triple-negative breast cancer and inflammatory breast cancer.

However, much of the mortality disparity can be ascribed to the cancer being diagnosed at a later, less treatable stage.

“Unfortunately, from experience — and now an increasing amount of empirical research — we know that the challenges are numerous and complex,” says David Arons, J.D., CEO of the National Brain Tumor Society. “To name just a few challenges, (we have) cost, geography (distance to primary and specialty care because of a paucity of providers in rural underserved areas), cultural competence and unconscious bias, language barriers, mistrust and technological divides.”

For many types of cancer, SDOH heavily influence prevention, early detection and mitigation of disease, adds Arons. For example, he says, easy access to physical exercise including bikeable and walkable places near one’s home and access to nutritious food are associated with reduced chances of childhood obesity, which has been linked to the development of a number of cancers later in life.

Arons lists some other risk factors for cancer that are rooted in SDOH. Lack of education, combined with the marketing efforts of
tobacco companies, leads to higher rates of smoking, which is a major risk factor for lung and other cancers. Living in neighborhoods with high levels of air or water pollution puts people at risk.

Interestingly, Arons says the SDOH that shape the contours of risk and mortality for many cancers in the U.S. do not appear to affect brain cancer rates. In fact, incidence rates are actually higher in highly educated White populations.

Niraj Mehta, M.D., a radiation oncologist at GenesisCare, an Australian cancer care company that has expanded to the U.S., says that the biggest challenges for people living in poorer neighborhoods is access to care and removing the impediments to getting that care. These include lack of transportation and childcare and limited or no time off for their treatments.

“Such patients often present at a later stage of diagnosis and are often afflicted with comorbidities such as poor nutrition and obesity,” he says. “Meaningful education needs to go well beyond typical ‘awareness’ efforts. Many for-profit private equity organizations and hospitals likely have minimal impact in these communities. Bottom-line organizations typically do not explore these communities in depth to understand their needs on cancer and health in general.” In Mehta’s opinion, one of the first steps to redressing disadvantageous SDOH is funding outreach efforts by local physicians who have the cultural and sociodemographic sensitivities needed to work with patients in those poor neighborhoods.

One area of disparity that has received a good deal of attention lately is enrollment in clinical trials. African Americans make up approximately 13% of the U.S. population, yet less than 2% to 3% of patients enrolled in cancer clinical trials are Black. Breastcancer.org, a nonprofit website for information about breast cancer, reported that between 2% and 9% of the participants in the trials that led to FDA approvals of four new breast cancer treatments in 2020 were Black. The proportion of Latino Americans was similarly small.

“This is one specific example, but it reflects the trend that we see of inadequate representation of minorities in clinical trials,” says Johnson of Cancer Treatment Centers of America in Atlanta.

, an American Society of Clinical Oncology journal, published a special package of 16 articles and editorials about cancer disparities. A number of them focused on the low enrollment of Black patients with cancer in clinical trials. A study of clinical trials that led to FDA approval of an oral cancer drug showed that just 889 of 35,933 (2.47%) patients in the trials were Black.

Vonetta M. Williams, M.D., Ph.D., a radiation oncologist at Memorial Sloan Kettering Cancer Center in New York, New York, says those numbers are very concerning because research has shown an association between clinical trial enrollment and improved outcomes. Williams says it is misguided to point to the attitudes of Black Americans as the reason for the low enrollment. “Many studies have cited mistrust (on the part) of Black Americans as a significant factor despite evidence showing that when offered enrollment, Black Americans consent to trial enrollment at similar rates to (those of) other groups,” she notes.

Ideas about how to increase enrollment of Black Americans in cancer clinical trials have proliferated. Williams says among the most promising are assessing trials’ inclusion and exclusion criteria to determine whether they are unnecessarily restrictive for certain populations. For example, many trials have cutoff points for the glomerular filtration rate, a measure of kidney function, that has led to the exclusion of Black Americans. Transportation and housing can also loom large as obstacles for some potential volunteers, notes Williams.

Lack of Medicaid coverage of the costs associated with participating in a trial has been another barrier for many Black patients. But at the beginning of 2022, the Clinical Treatment Act went into effect. It requires Medicaid to cover the routine costs of clinical trial participation for Medicaid enrollees with a life-threatening condition, including cancer.

Johnson says communication and connection between providers and minorities can help combat distrust of the health care system and improve health literacy.

Arons notes that the National Brain Tumor Society continues to argue for a policy that would include all National Cancer Institute-designated cancer centers as essential community providers in all marketplace health plans sold on the ACA exchanges. Lower-income individuals can sometimes end up in heath plans with slimmed-down provider networks that exclude the cancer centers, he says.

Keith Loria is a writer in the Washington, D.C., area who covers healthcare.

Articles

Research and discussion about the high cancer rates among Black Americans used to be dominated by genetics and the search for biological differences. Now attention has shifted to the social determinants of health.  

Reframing Race and Cancer

Research by University of Alberta investigators may have found the reason  HIV is so good at hiding from immune system and persisting in people’s bodies.

, Ph.D., the findings may answer a long-asked question.

Elahi and his colleagues researchers discovered that in patients with HIV, killer T cells (CD8+ T cells) have very little to none of a protein called CD73, which is necessary for migration and cell movement into the tissue. Without CD73, killer T cells cannot find and eliminate HIV-infected cells.

“This mechanism explains one potential reason for why HIV stays in human tissues forever,” Elahi said in a press release. “This provides us the opportunity to come up with potential new treatments that would help killer T cells migrate better to gain access to the infected cells in different tissues.”

The research team found that chronic inflammation results in increased levels of microRNAs, a type of RNA that can bind to messenger RNAs to block them from making CD73 protein. 

“We found this was causing the CD73 gene to be suppressed,” Elahi said in the press release.

The team noted that killer T cells play an important role against chronic viral infections, though their functional properties get compromised during the course of HIV infection.

CD73, is one of molecules that influences T cell functions, yet its role in the context of viral infections has never been well defined. With that in mind, the team analyzed the expression of CD73 on T cells in a cohort of 102 HIV-infected individuals. The group included those on antiretroviral therapy, those hadn’t been treated and long-term nonprogressors who were not on ART. 

“We found that the frequency of T cells expressing this molecule was markedly lower among different T cell subsets obtained from the blood of HIV-infected individuals,” Elahi said. “Notably, CD73 was decreased at the intracellular protein and gene levels.”

Furthermore, the researchers discovered that T cells expressing this molecule had impaired functional properties and elevated levels of homing receptors, which suggests a migratory advantage for these cells.

By revealing why HIV remains in human tissue even after antiretroviral therapy, the three-year project could open the door to new treatments that improve the immune system’s ability to eliminate not HIV. A byproduct may be a better understanding of multiple sclerosis and insight into why people with HIV have a lower risk of developing multiple sclerosis (MS)

“Our findings suggest that reduced or eliminated CD73 can be beneficial in HIV-infected individuals to protect them against MS; therefore, targeting CD73 could be a novel potential therapeutic marker for MS patients,” Elahi said. “Moreover, we found that the elevated level of ATP in the plasma of HIV-infected individuals is responsible for the upregulation of miRNA30b, 30c and 30e, resulting in reduced expression of CD73.”

In people with HIV, killer T cells (CD8+ T cells) lack a protein called CD73, which is necessary for migration and cell movement into the tissue. 

Study Explores Why People Can’t Get Rid of HIV

Presidential Advisory Council on HIV/AIDS

 recently made recommendations to scale up preexposure prophylaxis (PrEP) efforts.

 to HHS Secretary Xavier Becerra, the council urged the Biden administration to support the creation of a national PrEP program so all those who eligible for taking antiviral medications on a preventive basis have access to the medications and any associated services.

Only then, argued the council, would the administration’s Ending the HIV Epidemic in the U.S. (EHE) initiativebe considered a success.

“Establishing a national PrEP program will allow communities across the country to help meet the goal in the strategic plan to increase PrEP coverage to 50% by 2025,” co-chairs 

 wrote in the letter. “It will also help address ongoing racial and ethnic disparities and decrease new HIV infections.”

One of the chief recommendations was in addressing racial, ethnic and other inequities.


Carl Schmid, executive director of the HIV+Hepatitis Policy Institute, who contributed to the recommendations, notes this is vital as only about 1 in 4 of the approximately 1.2 million people who might benefit from PrEP are currently receiving it.

Data from 2019 show that 8% of Black people and 14%of Latino people who were eligible for PrEP were prescribed it compared with 63% of white people, according to the letter.

“In order to ensure PrEP uptake is increased among certain populations and communities, all PrEP programs and efforts must ﬁrst prioritize those communities and areas of the country that are most in need of PrEP and currently not utilizing it,” says Schmid.

The letter urges HHS to make sure that “all payers cover PrEP and associated services to the fullest extent possible under the law,” which includes zero cost sharing for those people with private insurance.

“We urge you to ensure insurers are in compliance with the guidance CCIIO (the Center for Consumer Information and Insurance Oversight) issued on July 19, 2021, and that new PrEP drugs, such as the long-acting injectable, be covered as quickly as legally possible,” the co-chairs wrote. “We also urge that similar guidance be issued for Medicaid and Medicare programs.”

The letter also says the national PrEP effort should take advantage of the 340B program: 

“The program should be designed to allow for the lower cost purchase of PrEP medications via the 340B drug pricing program, the utilization of generic PrEP, and free PrEP medication programs, PrEP peer navigation programs, PrEP marketing campaigns, and other culturally-relevant programs as appropriate,” the letter reads. “Funding of innovative strategies that effectively decrease PrEP usage disparities will be critical to close the widening racial and gender disparities of PrEP usage.”

The letter was unanimously adopted by council at its meeting, conducted virtually, on March 15, 2022. As of April 29, HHS has not delivered an official response. However, President Biden’s most recent budget proposal includes nationwide PrEP delivery program, along with significant boosts for HIV funding.

Letter from co-chairs Marlene McNeese and John Wiesman urges enforcement of coverage rules, including zero cost sharing for those with private insurance.

Presidential Council Urges HHS to Step Up PrEP Efforts

The FDA has approved a label update for Cabenuva, making the oral lead-in with cabotegravir and rilpivirine tablets optional.

Until the label change, oral cabotegravir and rilpivirine were to be taken for a month to assess tolerability to the medicines prior to starting, an injectable formulation of the two drugs.

, a senior vice president at ViiV Healthcare, the maker of Cabenuva, said in a press release that making the oral run-in period optional “provides a streamlined initiation process for the regimen by allowing people to start directly on long-acting injections and underscores ViiV Healthcare’s ongoing commitment to providing innovative treatment options.”

In addition, the FDA expanded Cabenuva’s label in March to include virologically suppressed adolescents 12 years of age or older and weighing at least 35 kg, marking the first time a long-acting HIV treatment is available for young people living with HIV.

, M.D., M.P.H., senior vice president, head of research and development for ViiV, says that Cabenuva is a meaningful option for the HIV community because it is the first complete treatment for HIV that does not include a daily pill.

With Cabenuva, people can go to their healthcare provider once a month, or every two months, to receive the injections and then can go on with their everyday lives without thinking about their HIV status, Smith noted./Some people worry about their pill bottle being found and their status being disclosed accidentally, so a long-acting treatment may ease those concerns.

“Many people face challenges with daily oral therapy and to offer a first-of-its-kind regimen for virologically suppressed adults that reduces dosing to as few as six times a year is a true innovation,” she says.

 reported in March that uptake of Cabenuva has been hindered by the COVID-19 pandemic and a centralized distribution system. Citing a report aboot a physician survey, the Fierce publication said that only 1% to 2% of patients are receiving the monthly injectable.

Cabenuva is comprised of two injectable medicines—ViiV Healthcare’s cabotegravir extended-release injectable suspension in a single-dose vial (200mg/mL) and rilpivirine extended-release injectable suspension in a single-dose vial (300mg/mL), a product of Janssen Sciences Ireland Unlimited Company, one of the Janssen Pharmaceutical Companies of Johnson & Johnson.

Cabotegravir is an integrase strand transfer inhibitor (INSTI), and rilpivirine is a non-nucleoside reverse transcriptase inhibitor (NNRTI); both medicines work by blocking enzymes that allow HIV to multiply in the body.

“INSTIs, like cabotegravir, block an HIV enzyme called integrase which can reduce the amount of HIV in the body,” Smith says. “Rilpivirine interferes with an enzyme called reverse transcriptase. By blocking reverse transcriptase and stopping reverse transcription, rilpivirine can stop the HIV virus from multiplying. The long-acting injectable formulations allow the medicines to stay in the body for longer, so people living with HIV can take it less frequently.”

“Based on our Cabenuva clinical trial data, we know some people living with HIV have been waiting for long-acting injectables,” Smith says. “Cabenuva dosed every two months was preferred by approximately nine out of every 10 participants, compared to daily oral cabotegravir and rilpivirine taken as the oral lead-in.”

As a leader in long-acting HIV regimens, ViiV Healthcare will continue to push the boundaries in its research and development efforts to make a difference in the lives of people living with HIV, she adds.

“Providing a broad range of treatment options is critical to improving health outcomes; no one therapy is going to work for everyone, so it’s important that people feel in control and that they have a choice when it comes to a treatment that fits within their lifestyle,” Smith says.

The oral run-in period for the injectable is now optional. The FDA also approved a label change that opens the door for adolescents to be treated with long-acting HIV treatment. 

Label Changes for Cabenuva, the Long-acting, Injectable HIV Treatment

On Jan. 3, 2022, the federal government officially renewed a declaration that the opioid epidemic is a public health crisis. Although the COVID-19 pandemic has overshadowed the opioid epidemic, the number of people in the U.S. dying from opioid overdoses has recently increased. According to preliminary data from the CDC, the number of overdose deaths from opioids rose to 75,673 in the 12-month period, ending in April 2021, and there was a 35% increase from 56,064 deaths recorded during the prior 12 months.

Federal government agencies and state health officials have taken various steps to clamp down on opioid prescribing in response to the epidemic. For example, most states have set a limit on the amounts of opioids physicians can prescribe. But some oncologists say the well-intentioned efforts have had the unintended consequence of preventing patients with cancer from getting essential pain relief.

“There has been so much attention in the media about the opioid epidemic — the overdoses and inappropriate prescribing. But many cancer doctors are seeing a spillover effect in our patients,” says Andrea Enzinger, M.D., an oncologist at the Dana-Farber Cancer Institute in Boston, whose research focuses on palliative care. “Patients are more fearful now. Those in end-stage cancer and in terrible pain are telling us they are afraid to use opioids and don’t want to get addicted.”

But patient apprehension is not the only issue. Enzinger notes there are some patients with cancer who want to use opioids but face multiple obstacles to getting them, whether that be because of pharmacies not having the medications in stock, prior authorization requirements or questioning by pharmacists. “Stricter opioid regulations have not intended for cancer to be the targets, and certainly not [those] who are dying,” she says. Enzinger also found there has been very little research into opioid use among patients with cancer during the opioid epidemic and the crackdown on opioid prescription. She decided to change that.

Enzinger is the lead author of a study on trends in opioid access among patients with cancer who have a poor prognosis that was published last year in the 

. Enzinger and her team analyzed a data set that included almost 280,000 Medicare beneficiaries with cancer who had a poor prognosis and who died between 2007 and 2017. When they looked at metrics of opioid utilization during the last 30 days of life, they identified a 34% decrease in opioid prescription fills and a 38% decrease in the total dose of opioids filled per decedent.

“That gives a good overall sense of what’s happening. A 38% decline in the amount of opioids prescribed in the last month of life per patient who died is a huge drop, particularly because there is a lot of literature that shows undertreatment of cancer pain has been a major problem,” Enzinger says. “If you are cutting the supply of opioids going to cancer patients, it’s a big problem.”

Enzinger and her colleagues also found a 50% reduction in filled prescriptions for long-acting opioids, which is not surprising, because they’ve been more tightly regulated than short-acting formulations because of their potential for abuse. But Enzinger says patients with severe cancer pain often need long-acting opioids.

“If you have a tumor sitting on your nerve, causing severe pain all the time, (and) if you don’t have a sustained-release medication, you’re chasing your pain all day and have to take something every two hours, even when you are trying to sleep,” Enzinger says. “It’s troubling.”

As opioid prescriptions fell, the results of Enzinger and her colleagues’ study showed that the proportion of patients making pain-related trips to the emergency department increased by 50%. “Among patients with terminal cancer, there have been substantial declines in opioid access and an increase in treatment of pain through the emergency department,” Enzinger says. “That suggests strongly that people are not able to manage their pain as well at home or do not have something in their medicine cabinet when having severe pain at night.”

As with all medications, opioids have benefits and risks. There is a risk of addiction, particularly for those with a prior history of substance use. Before prescribing, physicians are supposed to assess a person’s addiction risk with a variety of assessment tools. However, the risk of addiction for those with chronic pain and no prior history of substance use is not as common as some might think.

Nora Volkow, director of the National Institute of Drug Abuse, is on record as saying that, unlike tolerance and physical dependence, addiction is not a predictable result of opioid prescribing. “Addiction occurs in only a small percentage of persons who are exposed to opioids, even among those with preexisting vulnerabilities,” she said.

A study from the University of Michigan found that approximately 6% of patients who take opioids for the first time to relieve pain after surgery end up taking the medications for longer than clinically recommended. And dependency on opioids is a reality among patients with cancer. A number of studies have shown that because many patients with cancer require opioid analgesia (pain relief) for an extended period, they do, in fact, become dependent on the drug and will need higher and higher doses to get the same pain relief. If they stop taking the drug, they may experience withdrawal symptoms. But dependence and the need for greater doses are secondary concerns if patients are in pain and have a poor prognosis.

Navigating use the appropriate use of opioids is a challenge for patients and physicians, according to experts and countless physicians and patients. Many physicians would like to opioids used for a short while untill pain is treated in some other way — with PT, surgery or medications that are less likely to lead to dependency. But often that doesn’t happen. And many see a role for opioids in pain management for patients with cancer even if they are not at the end of life if the drugs help them be comfortable and can help with a good quality of life.

Cindy Steinberg, director of policy and advocacy at the U.S. Pain Foundation, a nonprofit organization sponsored by pharmaceutical companies, says that when pain persists for three months or longer, it becomes a disease of the nervous system and brain. “If it was caused by cancer, it could be from the disease itself damaging nerves or tissue, advanced disease causing increased damage, or the treatment itself, such as the type of chemotherapy or radiation causing damage,” she says.

“The best way to manage any type of chronic pain — including cancer pain — is through an individualized, multidisciplinary approach combining a number of treatment options,” Steinberg says. “There are many different medications that treat pain, and opioids are one important option in the toolbox, particularly for severe pain.”

Enzinger says efforts to combat the opioid epidemic must also balance the needs of patients with cancer who are experiencing pain.

“Patients face enough barriers as is,” she says. “(There is a) fear of being addicted or (some patients) think it’s a sign of weakness. Pharmacists asking why they are taking them, which sends the message they shouldn’t be using it. There needs to be more attention that this population needs protecting, even while we as a society are grappling with the opioid epidemic.” 

is a freelance writer in the Washington, D.C., area.

Patients with cancer who have a poor prognosis may face obstacles in accessing critical pain medications.

Has the Pendulum Swung Too Far Against the Use of Opioids?

A new study conducted by UCLA researchers Nina T. Harawa, Diane Tan, and Arleen A. Leibowitz, examined disparities in uptake of HIV pre-exposure prophylaxis (PrEP), using a cohort of California Medicaid enrollees. The 

“My coauthors and the Southern California HIV Policy Research Center have been doing research around PrEP for some time,” explains Harawa, which led her to wanting to explore both the policies and the more individual and couple/family-level factors that might impact uptake.

Past studies have identified substantial disparities in PrEP use, but few of those have done so in a group where everyone is able to access PrEP without prior authorization or other financial costs to the patient.

“PrEP is available to Medicaid beneficiaries in California, and Medi-Cal (California’s Medicaid program) covers one in five California adults,” Harawa says. “So, this was an ideal and a very large population in which to examine differences in uptake. Our goal was to measure these and then to determine if disparities by race and Hispanic origin could be explained by differences in the risk profiles or age distributions of the population.”

The researchers examined data from 2019 that had information on nearly 6 million Medicaid beneficiaries, ages 16-69. The data included classification by race. They found that uptake was highest for White and Black males and lowest for Hispanic males. Meanwhile, Black females had the highest uptake  and twice the rate of PrEP uptake of White females. 

“Rates for males far exceeded those for females,” says Harawa. “After taking into account age-differences between groups and a measure of need for PrEP, however, large disparities emerged, with White male beneficiaries having much better PrEP coverage than Black male and female or Hispanic male beneficiaries.”

Interestingly, beneficiaries, ages 16-24, had lower rates of PrEP uptake than those 25-34 or 35-69 even though this young group has a relatively high level of HIV risk.

Harawa and her colleagues did not use data on sexual or substance-use related behaviors among the Medicaid beneficiaries, but they made use of an external sample to assess whether differences in risk behaviors account for differences in PrEP uptake. 

“Our findings did not support this,” Harawa says. “After controlling for this measure of risk, which includes behaviors like number of sex partners and injection drug use among others, disparities by race and Hispanic origin did not change.”

It was obvious from the researchers’ conclusion that disparities in use of highly effective prevention strategies such as PrEP continue to exist, even among people enrolled in Medi-Cal, which makes PrEP available free and without prior authorization.

“It is also important to note that overall rates in this population were low,” Harawa says. “Focused outreach, education, and technical support to Medicaid agencies and Medicaid managed care organizations to increase PrEP use, as well as to expand Medicaid under the Affordable Care Act should be prioritized.”

HIV PrEP uptake was highest for White and Black males and lowest for Hispanic males. Meanwhile, Black females had the highest uptake and twice the rate of PrEP uptake of White females.  