Delivering Value-Based Cancer Care Across Different Populations

Treating patients with cancer encompasses more than just treating the cancer. During an Institute for Value-Based Medicine® event presented by The American Journal of Managed Care and The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, experts discussed the importance of thinking about the future, including how to get good outcomes as well as long-term survival with a focus on hematologic malignancies.

In the first presentation, Carrie Thompson, MD, associate fellowship director in the Division of Hematology/Oncology, Mayo Graduate School of Medicine, set the stage by discussing survivorship and what good survivorship means. There are more than 18 million cancer survivors in the United States, and 1.6 million of those are survivors of leukemia and lymphoma.¹

“We have this very large population of individuals who have been treated for malignancy in the United States, and we know that they have some pretty unique health issues as well as psychosocial issues,” Thompson said. “And our health care system is not yet set up optimally to care for this patient population.”

In the early stages of survivorship, there are a few issues: surveillance for relapse, psychosocial impacts of care, employment, and fertility. Further out, maybe a decade later, 2 primary issues to be aware of are cardiovascular disease and secondary malignancies.

“It’s important to remember that [treatment] is not a one-and-done,” she said. There are lifelong issues for these patients.

She focused on diffuse large B-cell lymphoma (DLBCL) because it is common and aggressive. Patients with DLBCL need treatment “at the time of diagnosis,” Thompson said. However, more than half of the patients are going to be cured and will need to be followed for relapse, because between 20% and 40% of patients treated for large B-cell lymphoma will have primary refractory disease or will relapse after treatment.²

Most relapses in DLBCL occur in the first and second years.2 Because relapse is still potentially curable, it is crucial to monitor patients for relapse. “We want to treat patients if they have a relapse, as they may…go on to live the rest of their lives if we can treat them appropriately,” Thompson said.

Years ago, when patients were being followed for relapse, they would receive scans every 3 months, but many relapses would happen in between, which raised the question of whether that many scans were even necessary. There is good evidence that surveillance scans have not been as useful as initially thought, she said.

In the case of indolent lymphomas, not all patients will need treatment at the time of diagnosis, but these patients do have an increased risk of lifelong relapse. There could be an argument that these patients are not cured and should be scanned more frequently, but this is an area where more data are needed.

However, retrospective studies have shown that only 6% of patients with follicular lymphoma had their relapse documented solely by routine CT scans.³ In addition, there was no difference in overall survival (OS) for patients whose relapse was detected clinically vs imaging.

In addition, there are downsides to surveillance scans, including radiation exposure, false positives, patient anxiety, and cost. One study found that routine surveillance plus PET/CT cost $4270 more than routine follow-up alone.⁴ Overall, it determined there were significant health care costs with little clinical utility.

Another downside is the anxiety and stress patients feel in the weeks leading up to their appointment for a surveillance scan, Thompson said. During the panel discussion at the end of the night, she added that some of the transparency being introduced has been a double-edged sword in this regard. On the one hand, transparency is good for patients to be involved in their care, but there are times when this access means patients see their results in a portal before seeing their doctor, and patients lack the expertise to interpret what they find, which leads to panic attacks.

As a result, national and international recommendations have caught up with the evidence and no longer recommend routine scans after someone is in complete remission, Thompson noted. How should patients be monitored instead?

“Really, it comes back to good clinical judgment and a good history, a good physical exam,” she said. “It’s talking to patients and monitoring symptoms.”

Andrew Hantel, MD, faculty member, Divisions of Leukemia and Population Sciences, Dana-Farber Cancer Institute, Harvard Medical School, followed with a conversation on disparities in clinical trials, as well as solutions to address these disparities. Historically, the standard of justice for clinical trial participation has been equality through process fairness, meaning the door is open to everyone. However, not everyone comes from the same background.

“The door that we’re offering open to people really takes a long time to get to for some people and has a lot more barriers when they get to it for others,” Hantel said. The focus has since shifted to equity so there is representation to ensure outcomes are the same for everyone. Without adequate representation in trials, it is unclear whether a drug will work in everyone the same way or only be successful in the subset studied.

There are multiple dimensions of disparity, although the broad constructs are race, ethnicity, sex, and age. Ultimately, these have to do with access to care, wealth, racism, and other factors that prevent historically marginalized groups from participating in clinical trials, he explained.

Geography is another major mediator of disparities. One study of pivotal clinical trial participation for adults with multiple myeloma and leukemia in the 2010s found that marginalized populations were not living near where the trials took place.⁵ “We know that trial site selection is a very important thing for pursuing diversity and clinical trials moving forward,” Hantel said.

Looking at eligibility criteria sheds further light on the structural reasons for the lack of trial enrollment. Analyzing common eligibility criteria has shown that Black patients are far more likely than White patients to be ineligible for a trial based on certain criteria, such as albumin, renal function, and diabetes.^6,7 In addition, Medicaid expansion increased trial enrollment,⁸ but there remain 10 states that have not adopted Medicaid expansion.⁹

Creating and implementing solutions is a “game of whack-a-mole” because of the multiple levels of influence and multiple domains of influence that lead to any one disparity. There are 4 categories of solutions:

• Policy solutions: The Food and Drug Omnibus Reform Act of 2022 empowers the FDA to mandate the development of a diversity action plan for pivotal trials, public workshops to enhance study diversity, and trial modernization and decentralization. There has also been an expansion of insurance to cover trial participation and new FDA support for trial eligibility criteria expansion.
• Health systems solutions: Workforce diversity through internal training programs and bidirectional external partnerships has helped to better reflect the patient population. Trial decentralization has led to community engagement and better nurse and lay navigation of trials.
• Trial design solutions: In addition to eligibility criteria expansion, there is greater participant involvement in trial designs to decrease burdensome activities and collect social determinant of health information. Sponsors are also increasing efforts by translating all patient-facing materials and providing participant remuneration, which could be risk- or milestone-based or cover transportation, parking, or lodging related to trial participation.
• Patient and provider solutions: Provider empowerment and awareness are being increased by giving them insight into how their patients in a trial are doing compared with the rest of their patients. In addition, implicit bias training and cultural- and language-appropriate education for patients allow them to make more empowered decisions early in their diagnosis.

During the panel discussion, Hantel noted that although pharmaceutical companies usually do not directly enroll people in trials, they do decide where the trial is, and there are some discussions that in order to improve diversity, maybe it should be mandated for trial sites to prove they can enroll a diverse patient population.

Alma Habib, MD, fellow, Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, further discussed disparities in hematologic malignancies. In addition to the structural barriers, individual factors, and health behaviors that Hantel discussed, Habib added biologic factors, such as differences in metabolism of drugs and in tumor biology as contributing to disparities in cancer care. In an abstract presented at the 2023 American Society of Clinical Oncology Annual Meeting, Habib and colleagues observed racial disparity in OS and cancer-specific mortality in 16 hematology malignancies.¹⁰

At 1, 3, 5, and 10 years, Black patients had shorter OS with an overall median OS of 90 months compared with 99 months for White patients.¹⁰ For cancer-specific mortality, Black patients had a higher cumulative incidence rate of cancer-specific death, with increasingly larger gaps at later time points.¹⁰ Furthermore, the disparity increased as the 5-year relative survival rate increased and the largest gaps were observed for the most treatable diseases.¹⁰ Throughout her presentation, Habib identified additional disparities in specific disease states based not just on race and ethnicity, but also mutation status, social deprivation index, delays in treatment, socioeconomic status, and immigration/refugee status.

Identifying the indicators of worse outcomes is crucial for developing interventions to overcome them, Habib said. There needs to be a better understanding of the genomic landscape for non-White patients considering most research is done in White populations.

Another intervention that can help address and minimize disparities involves culturally competent models of care that utilize nurse navigators and interpreters. Research has shown that nurse navigation can overcome socioeconomic disadvantages and lead to similar survival and trial participation between White patients and patients from a minority population.¹¹

Ultimately, addressing disparities requires a systems-level approach and it starts with the providers, Habib concluded. During the panel discussion at the end of the night, she noted the importance of knowing each individual patient’s barriers to care. Can they get to their appointments or are they having issues with transportation? Do they have access to childcare? Or are they having trouble affording their medications because they do not have insurance?

Finally, Sarah Wall, MD, assistant professor of clinical medicine, Division of Hematology, The Ohio State University Wexner Medical Center, addressed hematologic care for the geriatric population. With the rapidly aging US population, it is estimated that by 2030, 70% of cancers will be diagnosed in older adults.¹² However, despite the aging population, there is a shortage of gerontologists. “What that really amounts to is general oncology is geriatric oncology, and it will be for the foreseeable future,” Wall said.

According to data from the Surveillance, Epidemiology, and End Results database, the median age at diagnosis of chronic myeloid leukemia, acute myeloid leukemia, chronic lymphocytic leukemia, and non-Hodgkin lymphoma is between 65 and 70 years. In addition, survival is worse for older adults diagnosed with cancer compared with younger adults with the same cancers.¹³

Wall also noted that treatment decisions must consider the differences in an older person’s body that might affect clearance of drugs and the toxicities they experience. Interestingly, older individuals are the ones most likely to benefit from innovative therapies in hematologic malignancies, such as targeted therapies and oral agents, because these therapies are less intensive.

A study of the value of innovation in hematologic malignancies in 2012 found most fell below the $50,000 per quality-adjusted life-year (QALY) threshold and only 4 of the 44 incremental cost-effectiveness ratios were greater than $100,000 per QALY.¹⁴

Lastly, Wall highlighted the importance of end-of-life discussions in geriatric care. “It’s an important part of any conversation [for hematologic care], but particularly in an older adult population,” she said. 

References

1. Statistics and graphs. National Cancer Institute Division of Cancer Control and Population Sciences. Updated November 17, 2022. Accessed November 10, 2023. https://cancercontrol.cancer.gov/ocs/statistics
2. Maurer MJ, Ghesquières H, Jais JP, et al. Event-free survival at 24 months is a robust end point for disease-related outcome in diffuse large B-cell lymphoma treated with immunochemotherapy. J Clin Oncol. 2014;32(10):1066-1073. doi:10.1200/JCO.2013.51.5866
3. Oh YK, Ha CS, Samuels BI, Cabanillas F, Hess MA, Cox JD. Stages I-III follicular lymphoma: role of CT of the abdomen and pelvis in follow-up studies. Radiology. 1999;210(2):483-486. doi:10.1148/radiology.210.2.r99fe63483
4. Huntington SF, Svoboda J, Doshi JA. Cost-effectiveness analysis of routine surveillance imaging of patients with diffuse large B-cell lymphoma in first remission. J Clin Oncol. 2015;33(13):1467-1474. doi:10.1200/JCO.2014.58.5729
5. Casey M, Odhiambo L, Aggarwal N, et al. Are pivotal clinical trials for drugs approved for leukemias and multiple myeloma representative of the population at risk? J Clin Oncol. 2022;40(32):3719-3729. doi:10.1200/JCO.22.00504
6. Riner AN, Girma S, Vudatha V, et al. Eligibility criteria perpetuate disparities in enrollment and participation of Black patients in pancreatic cancer clinical trials. J Clin Oncol. 2022;40(20):2193-2202. doi:10.1200/JCO.21.02492
7. Sedrak MS, Ji J, Tiwari A, Mohile SG, Dale W, Le-Rademacher JG. Clinical trial enrollment, ineligibility, and reasons for decline in older vs younger patients with cancer in the National Cancer Institute Community Oncology Research Program. JAMA Netw Open. 2022;5(10):e2235714. doi:10.1001/jamanetworkopen.2022.35714
8. Unger JM, Ziao H, Vaidya R, LeBlanc M, Hershman DL. Medicaid expansion of the Patient Protection and Affordable Care Act and participation of patients with Medicaid in cancer clinical trials. JAMA Oncol. 2023;9(10):1371-1379. doi:10.1001/jamaoncol.2023.2800
9. Status of state Medicaid expansion decisions: interactive map. Kaiser Family Foundation. October 4, 2023. Accessed November 12, 2023. https://www.kff.org/medicaid/issue-brief/status-of-state-medicaid-expansion-decisions-interactive-map/
10. Habib A, Huang Y, Paskett ED, Devarakonda SS, Fisher JL, Kittai A. Evaluating depth of disparities in relation to relative survival rates: analysis of SEER data. J Clin Oncol. 2023;41(suppl 16):6602. doi:10.1200/JCO.2023.41.16_suppl.6602
11. Hu B, Boselli D, Pye LM, et al. Equal access to care and nurse navigation leads to equitable outcomes for minorities with aggressive large B-cell lymphoma. Cancer. 2021;127(21):3991-3997. doi:10.1002/cncr.33779
12. White MC, Holman DM, Boehm JE, Peipins LA, Grossman M, Henley SJ. Age and cancer risk: a potentially modifiable relationship. Am J Prev Med. 2014;46(3 suppl 1):S7-S15. doi:10.1016/j.amepre.2013.10.029
13. Krok-Schoen JL, Fisher JL, Stephens JA, et al. Incidence and survival of hematological cancers among adults ages≥75 years. Cancer Med. 2018;7(7):3425-3433. doi:10.1002/cam4.1461
14. Saret CJ, Winn AN, Shah G, et al. Value of innovation in hematologic malignancies: a systematic review of published cost-effectiveness analyses. Blood. 2015;125(12):1866-1869. doi:10.1182/blood-2014-07-592832