Medical World News: Policy, Clinical, and Managed Care Updates

August 17, 2019

Chronic pain, obesity and cancer, multiple myeloma patterns, pancreatic cancer screening updates, and more.

POLICY UPDATES

UK Cancer Group Warns That Obesity Is Overtaking Smoking as Disease Driver

Although smoking cigarettes is considered the most prevalent—yet preventable—cancer risk, new data suggest that people who are obese now outnumber people who smoke, and excess weight now causes more cases of certain cancers than smoking in the United Kingdom.

According to recent data, nearly one-third of UK adults are obese and overweight, which now holds a greater risk of developing 4 types of cancer compared with smoking.

“As smoking rates fall and obesity rates rise, we can clearly see the impact on a national health crisis when the government puts policies in place—and when it puts its head in the sand,” Michelle Mitchell, Cancer Research UK’s chief executive, said in a statement. “Scientists have so far identified that obesity causes 13 types of cancer, but the mechanisms aren’t fully understood. So further research is needed to find out more about the ways extra body fat can lead to cancer.”1

In the United Kingdom, data show that each year, excess weight causes around 1900 more cases of bowel cancer than smoking does. Similarly, there are 1400 more cases of kidney cancer, 460 more cases of ovarian cancer, and 180 more of liver cancer each year.2

Comparatively, in the United States, in 2011 to 2014, nearly 70% of adults were overweight or obese and more than one-third were obese, according to the National Cancer Institute.3 In the United States, obesity is linked to increased risks of endometrial cancer, esophageal adenocarcinoma, gastric cardia cancer, liver cancer ,and others. Additionally, smoking has steadily declined in the United States since the mid-1960s, whereas obesity has been rising, according to America’s Health Rankings.4

“There isn’t a silver bullet to reduce obesity, but the huge fall in smoking over the years—partly thanks to advertising and environmental bans—shows that government-led change works. It was needed to tackle sky-high smoking rates and now the same is true for obesity,” noted Linda Bauld, professor of public health at The University of Edinburgh in Scotland. “The world we live in doesn’t make it easy to be healthy, and we need government action to fix that, but people can also make changes themselves—small things like swapping junk food for healthier options and keeping active can all add up to help reduce cancer risk.”

Cancer Research UK launched a campaign to increase the awareness of the obesity-related cancer risk. The campaign suggests that policy change can help people form healthier habits, and the hope is that the government will act on this initiative to reduce childhood obesity rates by 50% by 2030.

References

1. Obese people outnumber smokers two to one [press release]. London, UK: Cancer Research UK; July 3, 2019. cancerresearchuk.org/about-us/cancer-news/press-release/2019-07-03-obese-people-outnumber-smokers-twoto-one. Accessed July 17, 2019.

2. Brown KF, Rumgay H, Dunlop C, et al. The fraction of cancer attributable to modifiable risk factors in England, Wales, Scotland, Northern Ireland, and the United Kingdom in 2015. Br J Cancer. 2018;118(8):1130-1141. doi: 10.1038/s41416-018-0029-6.

3. Obesity and cancer. National Cancer Institute website. cancer.gov/about-cancer/causes-prevention/risk/obesity/obesity-fact-sheet. Updated January 17, 2017. Accessed July 18, 2019.

4. 2016 annual report: smoking and obesity—a public health success and challenge. America’s Health Rankings website. americashealthrankings.org/learn/reports/2016-annual-report/spotlight-smoking. Published 2016. Accessed July 18, 2019.

Nearly 5.4 Million Cancer Survivors Experience Chronic Pain

Chronic pain, one of the most common long-term effects of cancer treatment, is associated with lower quality of life, lower adherence to treatment, and higher healthcare costs. According to a new research letter, as the number of cancer survivors continues to grow rapidly in the United States, 5.39 million cancer survivors experience chronic pain.

In a study published in JAMA Oncology, investigators reported that about 1 in 3 cancer survivors reported having chronic pain. One in 6 reported experiencing high-impact chronic pain that restricts daily functioning, representing 2.51 million survivors. According to the investigators, these rates are nearly double that of the general population, which suggests the presence of unmet needs among the survivorship community.

These rates were determined from data extracted from the National Health Interview Survey from 2016 to 2017. The investigators identified 4526 cancer survivors from 59,770 survey participants. Among these survivors, 1648 (34.6%) reported having chronic pain; 768 (16.1%), high-impact chronic pain.

There were no significant differences in the prevalence of chronic pain or high-impact chronic pain based on age, sex, marital status, or region. However, there was a higher prevalence of both chronic and high-impact chronic pain among survivors with less than a high school education (39.2% for chronic pain, 18.5% for high-impact chronic pain), low household income (44.6% and 22.8%, respectively), public insurance for those aged 18 to 64 years (43.6% and 27.1%, respectively), and no paid employment (38.5% and 20.4%, respectively).

“Because socioeconomic status and employment are associated with insurance coverage and access to care in the United States, the patterns of chronic pain that we observed in cancer survivors may be explained by barriers to cancer care and pain management, as well as by the type and extent of cancer treatment received,” wrote the authors.

They noted that the absence of significant differences in pain based on sex contrasts with the general perception of higher prevalence of pain in women compared with men. This could be because of insufficient statistical power from the limited sample size or because cancer-induced pain in both sex groups might have diluted the relative difference, they wrote.

Across cancer types, the prevalence of chronic pain was highest among survivors of bone (54%), kidney (52.3%), throat-pharynx (47.9%), and uterine (44.5%) cancers. Prevalence of chronic and high-impact chronic pain did not significantly differ based on time since diagnosis.

CLINICAL UPDATES

Blinatumomab Reduces MRD Prior to HCT in Pediatric Patients With B-ALL

When given prior to hematopoietic cell transplantation (HCT), blinatumomab reduces minimal residual disease (MRD) and results in favorable leukemia-free survival, toxicity, and overall survival (OS) in pediatric patients with relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL), according to study results appearing in the journal Blood Advances.

The findings have important implications because patients undergoing HCT with MRD are often at significant risk of relapse, but it has been unclear how to best eliminate MRD prior to transplantation. Approaches that used chemotherapy have yielded mixed results and added toxicity, including infection and organ injury, which can delay or prevent HCT.

Blinatumomab, which is approved for patients with relapsed or refractory B-ALL or persistent MRD, is designed to recognize the lymphoid marker CD19 that is expressed by most B-ALL.

Out of 15 patients aged 0 to 21 years included in the study, 14 were MRD negative following treatment with blinatumomab. Prior to treatment, the median MRD level was 0.57% of the mononuclear cell compartment. The majority (80%) of patients, who were recruited from 5 Foundation for the Accreditation of Cellular Therapy—accredited pediatric HCT centers, received a 28-day course of blinatumomab at 15 μg/m2 per day between 2016 and 2018. Two patients had their initial treatment cycle shortened in order to start HCT preparative therapy, and the remaining patients received 2 courses of the treatment for 66 days.

According to the authors, patients proceeded to definitive HCT therapy without delay, in some cases starting the myeloablative preparative regimen just a few hours after completing their blinatumomab infusion. “In patients where the unrelated donor was not readily available, this approach provided the advantage of a low-toxicity therapeutic bridge while waiting for an alternative donor,” wrote the authors.

All the patients had successful neutrophil engraftment in the expected time frame, with a median time frame of 19 days. At 1 year, OS was 93.3%, and there was no transplant-related mortality in the first 100 days. “Because blinatumomab activates the immune system and can result in cytokine release syndrome, there is some concern that any lymphocyte activation prior to HCT could negatively influence donor engraftment or perhaps cause greater rates of GVHD [graft-vs-host disease],” wrote the investigators. “However, all patients successfully engrafted and overall rates of grades 2 to 4 acute GVHD and chronic GVHD were low, despite alternative

donors being the prominent stem cell source.”

In the 30 days following HCT, 1 patient experienced any significant HCT-related complication. Two (14.3%) of the 14 patients who became MRD negative experienced grade 2 or 3 acute GVHD, and 3 (21.4%) experienced extensive chronic GVHD.

Four patients experienced a relapse of CD19-positive ALL at a median time of 355 days post HCT, but all 4 successfully achieved subsequent remission following CD19 positive—direct therapy and sustained a complete response at the time of the report.

Reference

Keating AK, Gossai N, Philips CL, et al. Reducing minimal residual disease with blinatumomab prior to HCT for pediatric patients with acute lymphoblastic leukemia. Blood Adv. 2019;3(13):1926-1929. doi: 10.1182/bloodadvances.2018025726.

Investigators Identify Multiple Myeloma Treatment Patterns by Age and Region

With 40% of patients with newly diagnosed multiple myeloma (NDMM) or relapsed/refractory multiple myeloma (RRMM) ineligible for clinical trials, outcomes in elderly or frail patients are unclear. What data are available suggest that these patients have poorer outcomes, which may be a result of using less-aggressive treatments or because they have comorbidities or poor tolerance to therapies.

An abstract presented at the 24th European Hematology Association Congress, held June 13 to 16, 2019, in Amsterdam, the Netherlands, evaluated real-world treatment patterns by region and age to better understand and address these issues.

The investigators used data from INSIGHT MM, a global, prospective, noninterventional, observational study. Patients were enrolled from 16 countries and followed prospectively for at least 5 years, with data collected at baseline and every 3 months.

The enrolled patients included 1495 with NDMM and 1263 with RRMM. More than half (56%) of those with NDMM and just less than half (46%) of those with RRMM were younger than 66 years, respectively; 33% and 35% were between 66 and 75 years; and 14% and 19% were older than 75 years.

In patients who had new diagnoses and were younger than 66 years or between ages 66 and 75, triplet therapies were the top 3 most common regimens, whereas doublets were more common (2 of the top 3) in patients older than 75 years. However, for each age group, across all regions, the most commonly used treatment was bortezomib, cyclophosphamide, and dexamethasone (VCd). In Europe, VCd was the most commonly used among patients 66 years and older, whereas bortezomib, thalidomide, and dexamethasone was used most for patients younger than 66 years. In the United States, bortezomib, lenalidomide, and dexamethasone was the most commonly used for all age groups.

A similar pattern emerged in patients with RRMM, with younger patients more likely to use triplet therapy compared with older ones. However, there is greater treatment heterogeneity in patients with RRMM, which the investigators attributed to the greater number of novel treatments available in the setting. Although the second and third most commonly used regimens varied greatly, there was consistency at the top: Lenalidomide and dexamethasone was most commonly used across all age groups in Europe and for patients 75 years or younger in the United States. Patients older than 75 years were most commonly prescribed carfilzomib and dexamethasone.

“Regulatory reasons may also contribute to the greater number of regimens for RRMM, as drugs are generally first approved in this setting before moving to NDMM,” the authors noted.

Reference

MANAGED CARE UPDATES

USPSTF: Screen Those at High Risk for Pancreatic Cancer

Chari A, Weisel KC, Usmani SZ, et al. Evolving treatment patterns in multiple myeloma (MM) differ by age and region: analysis from INSIGHT MM, a global, prospective, observational study. Poster presented at: 24th European Hematology Association Congress; June 13-16, 2019; Amsterdam, the Netherlands. Abstract PF601.The US Preventive Services Task Force (USPSTF) has kept its recommendation against screening everyone for pancreatic cancer, but for the first time said this does not apply to people with known genetic syndromes of family history of the deadly cancer. It’s an important shift for the diagnosis of a disease that, while still relatively rare, is becoming a leading cause of cancer death in the United States as survival rates improve for other types. USPSTF’s August 6, 2019, recommendation of “D” for population-wide screening for pancreatic cancer, published in JAMA Internal Medicine,1 means the evidence shows that screening in asymptomatic adults demonstrates moderate or high certainty of no net benefit or that harms will outweigh benefits.

An accompanying editorial in JAMA Surgery states that this conclusion is not a surprise, given the potential for false-positive results and harms of treatment.2

This is the first update of USPSTF recommendations on pancreatic cancer screenings in 15 years. It is now the fourth-leading cause of cancer death, although it is the ninth most common cancer among women and the 10th most common among men.3

Pancreatic cancer typically produces no symptoms early on, so it’s frequently caught in later stages, when surgery may no longer be possible. Thus, the 5-year survival for pancreatic cancer remains a dismal 9% overall, although the rate is 34% for localized cancer.3 With those statistics, why not screen everyone? As Ralph H. Hruban, MD, and Keith D. Lillemoe, MD, note in their editorial, even the most sensitive test (99% specificity) will generate a number of false positives when applied to the general population, leading to more testing and perhaps surgery. Still, Hruban and Lillemoe found hope in the task force’s acknowledgment that evidence for the usefulness of genetic biomarkers in pancreatic cancer is rapidly improving. “Populations with significantly increased risk can now be targeted for screening, greatly increasing their positive pretest probability,” they write.

The Pancreatic Cancer Action Network (PanCAN) took note of critical language changes for people with high risk. “USPSTF has made an important change to its definition of the ‘general population.’ For the first time, the USPSTF has noted their recommendation does not apply to people with a known inherited genetic syndrome or strong family history of pancreatic cancer. “Instead, they are encouraged to participate in surveillance programs at ‘experienced centers, ideally under research conditions,’” according to the advocacy group’s website.4

PanCAN took note of the recent update to National Comprehensive Cancer Network guidelines, which called for all pancreatic cancer patients to receive germline cancer screening.

References

1. US Preventive Services Task Force. Screening for pancreatic cancer: US Preventive Services Task Force reaffirmation recommendation statement. JAMA. 2019;322(5):438-444. doi:10.1001/jama.2019.10232.

2. Hruban RH, Lillemoe KD. Screening for pancreatic cancer gets a D, but the student is improving [published online August 6, 2019]. JAMA Surg. doi:10.1001/jamasurg.2019.2832.

3. Pancreatic cancer statistics. Cancer.Net cancer.net/cancer-types/pancreatic-cancer/statistics. Updated January 2019. Accessed August 7, 2019.

4. Rosenzweig A. Task force updates pancreatic screening recommendations. Pancreatic Cancer Action Network website. pancan.org/news/task-force-updates-pancreatic-cancer-screening-recommendations/. Updated August 6, 2019. Accessed August 7, 2019.

CMS Proposes Bundled Payments for Radiation Oncology

After months of alluding to an upcoming change, on July 15, 2019, CMS proposed implementing bundled payments for radiation oncology. The Radiation Oncology (RO) Model could come as soon as January 1, 2020, covering 17 different types of cancer.1

The RO Model would be regulated by the Center for Medicare and Medicaid Innovation. Under the model, CMS would make bundled payments to physician group practices, hospital outpatient departments, and freestanding radiation centers that would cover radiation therapy spanning a 90-day episode. The model would be mandatory in certain parts of the country to determine whether prospective site-neutral, episode-based payments could reduce Medicare costs and improve the quality of care. In the proposed rule, CMS wrote that the agency believes having a mandatory model will offer access to more complete evidence of the impact of the model.

The model would qualify as an advanced alternative payment model (APM) and a Merit-based Incentive Payment System APM and would have a performance period of 5 years, beginning either January 1 or April 1, 2020, and ending December 31, 2024. HHS Secretary Alex Azar first hinted in November 2018 that a mandatory payment model for radiation therapy was coming, saying that the administration was revisiting previously scrapped mandatory models in cardiac care and new and improved episode-based models in other areas, such as radiation oncology.2 CMS cited 3 reasons for the need for payment reform in radiation oncology: lack of site neutrality for payments, incentives that encourage volume over value, and coding and payment challenges.

“This patient-centric and provider-focused model would improve the quality of care cancer patients receive and improve patient experience by rewarding high-quality patient-centered care that results in better outcomes through a prospective, episode-based payment methodology,” CMS said in a statement.1 The payments would be split into 2 parts: a professional component to cover services that may be provided only by a physician and a technical component to cover services not provided by a physician, including the provision of equipment, supplies, personnel, and costs related to radiotherapy services. All 17 cancer types that would be incorporated in the model are commonly treated with radiation, make up the majority of cancer incidence, and have demonstrated pricing stability. These include anal, bladder, breast, cervical, colorectal, head and cancer, lung, pancreatic, and prostate cancers.

Following the announcement, organizations responded with praise for a value-based model in radiation oncology but caution over the model being mandatory. Paul Harari, MD, FASTRO, chair of the American Society for Radiation Oncology (ASTRO), said in a statement that the model “is a step forward in allowing the nation’s 4500 radiation oncologists to participate in the transition to value-based care that improves outcomes for cancer patients.”3 He added that ASTRO will submit comments on the specifics of the model, including the requirements for certain radiation oncology groups to participate.

The Community Oncology Alliance released a statement voicing its concern over the mandatory model, writing that although it believes the model includes a much-needed policy proposal to implement site-neutral payments, it “has deep reservations and fundamental opposition to a proposed mandatory or ‘required’ CMS Innovation Center (CMMI) model.”4

References

1. Radiation Oncology Model. CMS website. innovation.cms.gov/initiatives/radiation-oncology-model/. Updated July 15, 2019. Accessed July 18, 2019.

2. Caffrey M, Inserro A. Azar announces mandatory oncology payment model is coming. The American Journal of Managed Care® website. ajmc.com/newsroom/azar-announces-mandatory-oncology-payment-model-is-coming. Published November 8, 2018. Accessed July 18, 2019.

3. Proposed radiation oncology alternative payment model to test new approach to cancer treatment payments [press release]. Arlington, VA: American Society for Radiation Oncology; July 10, 2019. astro.org/News-and-Publications/News-and-Media-Center/News-Releases/2019/APM-statement. Accessed July 18, 2019.

4. COA statement on proposed radiation oncology alternative payment model [press release]. Washington, DC: Community Oncology Alliance; July 11, 2019. communityoncology.org/coa-statement-on-proposed-radiation-oncology-alternative-payment-model/. Accessed July 18, 2019.