Home Infusion Trend Stirs Debate

Nathan R. Handley, MD, MBA

The COVID-19 pandemic spurred the launching or expansion of in-home cancer therapy infusion programs at several oncology centers around the United States, drawing a surge of interest throughout the field as well as opposition from oncologists who are concerned about the implications for patient safety and the potential impact on community practices that provide in-house infusion services.

In addition to addressing COVID-19–related safety concerns, the potential cost savings from moving the site of care to patients’ homes has stoked interest from payers and specialty pharmacy companies. But Nathan R. Handley, MD, MBA, a medical oncologist at Sidney Kimmel Cancer Center — Jefferson Health in Philadelphia, Pennsylvania, said the primary driver for his center’s in-home infusion program is patient convenience.

“The goal is really to develop a cancer care delivery system that is more responsive to an individual patient’s needs,” Handley said. He helps run Jefferson’s in-home chemotherapy initiative, which was started in 2019. “Coming into the infusion center can be very burdensome, especially if someone is coming to our downtown campus. If it’s an hour infusion, it’s not an hour of time; it’s like half a day. They have to get ready, they drive in, they park, they get bloodwork, and then they wait, and wait, and wait, and they get their infusion.

“If they can minimally disrupt their life, that creates opportunities to have time with family, more time with work, more time to focus on priorities other than the physical act of getting their chemotherapy. Our goal is not for this to be something that everyone gets, but something we can have a conversation about with lots of patients.”

Although the concept of in-home infusion therapy is gaining adherents, the American Society of Clinical Oncology (ASCO) has expressed reservations about the safety of routinely administering anticancer drugs in patients’ homes and the Community Oncology Alliance (COA) has declared its staunch opposition. Neither group opposes portable therapy delivery through implantable infusion devices.^1,2

When COVID-19 started to disrupt medical care in the spring of 2020, COA issued a statement saying the organization “fundamentally opposes home infusion of chemotherapy, cancer immunotherapy, and cancer treatment supportive drugs because of serious patient safety concerns.”²

As drug delivery systems continue to evolve, the debate over in-home infusion is likely to intensify. Industry analysts anticipate steady expansion in North American markets for home infusion therapies, with chemotherapy being one of the strongest drivers of growth.^3,4

Additionally, an increase in FDA approvals for monoclonal antibodies administered via subcutaneous vs intravenous infusion, including several for treating patients with cancer, may contribute to demand for home-based care.5,6 In June 2020, the FDA approved Phesgo, a subcutaneous formulation that incorporates pertuzumab (Perjeta) and trastuzumab (Herceptin) with hyaluronidase–zzxf for the treatment of patients with HER2-positive breast cancer in combination with chemotherapy.⁷ The agency stated that “a qualified health care professional” can administer Phesgo in the patient’s home once the chemotherapy portion of the treatment is completed.⁸

Changing Chemotherapy Landscape

Home infusion of cancer therapy is not a new idea. Take-home chemotherapy has been available for decades, principally in the form of ambulatory pumps infusing 5-fluorouracil (5-FU).^9,10 To receive ambulatory therapy with 5-FU, patients are connected to the pump at a clinic, carry it with them for 48 hours, and return to the center to be disconnected or to receive a new pump. Handley said some centers also have been providing home infusion of high-dose cytarabine (HiDAC) or the 5-drug combination EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin) for patients with hematologic malignancies.

Although portable infusion devices have become established in oncology care, home infusion of therapies represent another step. Starting in the 1980s, infusion therapy has shifted from hospitals to physician-owned or hospital-affiliated outpatient centers.² Some experts regard in-home infusions as an innovation in the development of chemotherapy.⁹

Globally, an estimated 5% to 10% of patients with cancer receive oncology treatments at home.¹¹ However, the practice of in-home infusional therapy has not been widely adopted in the United States.

That is starting to change. In 2019, both Jefferson and the University of Pennsylvania/ Penn Medicine, also in Philadelphia, launched pilot programs that send nurses to the homes of patients with cancer to administer leuprolide (Lupron) injections or set up infusions of a number of different drugs.

Those efforts accelerated in 2020 as the medical centers sought to keep patients with cancer out of clinics and to free up their resources for patients with COVID-19.

Penn provided cancer treatments at home for 1500 patients in 2020 and expects to serve at least that number this year, said Callie Scott, MSc, managing director of the Penn Center for Cancer Care Innovation at the Abramson Cancer Center.

The center administers more than 30 different therapies in the home, including leuprolide, 5-FU, EPOCH, pembrolizumab (Keytruda), nivolumab (Opdivo), bortezomib (Velcade), rituximab (Rituxan), carboplatin, carfilzomib (Kyprolis), cisplatin, cladribine, and cytarabine, Scott said.

Penn’s nurses also administer fludarabine phosphate, ifosfamide (Ifex), interferon alfa-2b, irinotecan, methotrexate sodium, mitoxantrone HCl, omacetaxine mepesuccinate (Synribo), trabectedin (Yondelis), zoledronic acid, denosumab, pegfilgrastim, f ilgrastim, aldesleukin, cidofovir, and others in patients’ homes.

Handley said Jefferson’s nurses administered in-home infusions of HiDAC and EPOCH to approximately a dozen patients last year and the number is expected to grow. Jefferson’s nurses also have been giving more leuprolide injections at patients’ homes than before the pandemic.

Several other centers have recently launched or expanded home chemotherapy programs, including Fairview Health Services in Minneapolis, Minnesota.¹²

David M. Gill, MD, an oncologist at Intermountain Healthcare in Salt Lake City, Utah, said he hopes to start providing in-home chemotherapy and immunotherapy in October after delays relating to the pandemic and reimbursement issues. Oncologists at Moffitt Cancer Center in Tampa, Florida, also are considering creating a program, according to a Moffitt spokesperson.

Rogel Cancer Center at University of Michigan Health in Ann Arbor has expanded its HomeMed infusion program, which now serves more than 200 patients at a time, according to Tricia Sirois, PharmD, assistant director of pharmacy for home care services.

Some pharmacy companies are encouraging patients with cancer to try home treatment. In November 2020, Optum Infusion Pharmacy, a UnitedHealthcare affiliate, began covering home infusion therapy, including monoclonal antibodies and immunotherapies, for the insurer’s commercial members in Florida.¹³ Earlier this year CVS Health’s infusion business, Coram, announced an agreement with Cancer Treatment Centers of America to administer home treatments to eligible patients, starting in Atlanta, Georgia.¹⁴

In July 2020, health insurer Aetna, a subsidiary of CVS Health, began covering outpatient and home administration of several immune checkpoint inhibitor monotherapies for maintenance regimens, including nivolumab, pembrolizumab, ipilimumab (Yervoy), durvalumab (Imfinzi), cemiplimab (Libtayo), avelumab (Bavencio), and atezolizumab (Tecentriq).¹⁵ The company cited COVID-19–related concerns and potential savings on drug spending and administration exceeding 50%.

Some anticancer regimens are suitable for in-home infusion but others are not, according to a National Comprehensive Cancer Network (NCCN) working group.¹⁶ An NCCN committee, cochaired by Timothy Kubal, MD, MBA, of Moffitt Cancer Center, has been trying since 2015 to make the US chemotherapy delivery system more efficient. The infusion toolkit was revised in light of the pandemic to consider which of 12 regimens currently being provided on an outpatient basis are appropriate for in-home delivery.^16,17

Sparse Safety Data

Handley said his advocacy for in-home chemotherapy was inspired by Hospital at Home initiatives in the United States and other countries that deploy multidisciplinary care teams to treat patients with congestive heart failure exacerbations, cellulitis, chronic obstructive pulmonary disease flares, or pneumonia. Findings from studies of a 20-year-old program at Johns Hopkins Medicine in Baltimore, Maryland, found that the approach shortened length of stay by one-third, lowered cost relative to usual inpatient care by more than 30%, and demonstrated improved patient satisfaction with the overall care experience.^18,19

Many investigators have evaluated the benefits of in-home care in general, but studies focused specifically on home infusion of cancer therapies other than 5-FU are rare, particularly in the United States, and most include small numbers of patients.

Handley and other proponents of home cancer therapy cite a 2012 observational study from Switzerland that analyzed 200 days of home care, representing 46 treatment cycles of intensive chemotherapy in 17 patients.²⁰ Drugs were administered through a portable, programmable pump via an implantable catheter. The main end points were safety, quality of life as measured by the Functional Living IndexCancer (FLIC), satisfaction of patients and relatives, and cost.

The drugs administered during the study included standard ICE (ifosfamide, carboplatin, and etoposide), modified BEACOPP (etoposide, doxorubicin, cyclophosphamide), BEAM (carmustine, etoposide, cytarabine, and melphalan), VAD (vincristine, doxorubicin, and dexamethasone), melphalan, and other intensive chemotherapy regimens.

Investigators reported that FLIC scores remained constant throughout the study and all patients rated home care as very satisfactory or satisfactory. Patient benefits of home care included increased comfort and freedom, whereas relatives cited better tolerance and less asthenia. An analysis of the mean daily direct costs of care including overhead showed that home care resulted in a 53% cost benefit compared with inpatient hospital treatment (€420 ± 120/day vs €896 ± 165/ day), mostly because the use of an automated pump reduced nursing involvement and paraclinical tests.

Technical problems complicated 2 cycles of therapy, necessitating hospitalization for a total of 5 days. Three major medical complications (heart failure, angina pectoris, and major allergic reaction) could be managed at home, as could grades 1 and 2 nausea and vomiting, which occurred in 36% of patients.

Scott also cited 2 studies on adverse events (AEs) during home infusion. In one, a retrospective study of implantable venous access devices used at a Veterans Affairs medical center in Arkansas, there were no differences in complications for patients receiving home-based vs hospital-based chemotherapy administration.²¹ In the other study, investigators evaluated the safety of home administration of adenosine 5′-triphosphate to promote nutritional status and survival in 51 patients with preterminal cancer in the Netherlands.22 They found that the majority of infusions (63%) resulted in no AEs and the AEs that did appear were mild and transient.

In a 2016 analysis of results from 54 studies, investigators found there were often no differences in quality of life or satisfaction or in health care utilization metrics such as emergency room visits, between in-home chemotherapy and hospital or outpatient therapy.²³ Any differences that were found were in favor of home care. Findings on financial impact varied according to how costs were calculated and other factors, with some studies finding no difference and others a significant cost benefit for home care over inpatient treatment.

An accompanying analysis of 7 home chemotherapy programs in the United States, Canada, United Kingdom, and Australia found no major safety incidents and high patient and family satisfaction, with 5-FU being the drug offered most frequently.

Connie Sullivan, BSPharm, president and CEO of the National Home Infusion Association (NHIA), said that her organization has been collecting data on AEs during home infusion and will release a report in the next several months. “There is no evidence that patients who do chemotherapy at home have higher rates of adverse events, and they have very high rates of patient satisfaction with the service,” she said.

The lack of robust data has been noted by those opposed to chemotherapy infusion initiated in patients’ homes, including ASCO. “There is a paucity of evidence directly comparing the safety of chemotherapy infusions in the home and outpatient settings. The vast majority of the literature examines home infusion in general, which is of limited utility given the toxicity and hazardous materials specific to chemotherapy,” the ASCO board of directors said in June 2020 position statement.¹

“Although ASCO understands the desire for increased flexibility for patients, serious adverse events do occur and require special expertise of oncologists to either prevent or address them during drug preparation and administration,” the directors stated. In voicing their objections in a position statement on home infusion, COA officials stressed the potential for serious AEs. “Home infusion by a provider—who may or may not be a trained oncology nurse—and may not recognize and be prepared to treat any adverse reactions—whether simple, significant, or even lethal—that may occur as a common part of an infusion of cancer drugs is of significant concern,” COA officials said. “…It is not an appropriate option for patients with cancer.”²

Jefferson and Penn screen patients for suitability, do not give taxanes or other drugs that have a high risk of severe adverse reactions, and administer at least 1 round of therapy in a clinic before approving a patient for home infusion. However, those safeguards are not enough to convince community oncologists such as COA vice president Miriam J. Atkins, MD, FACP, of Augusta Oncology Associates in Georgia.

“It may look good in theory, on paper, but in my office we’ve had patients have severe reactions. We’ve had patients die within a minute of an infusion. Some places are thinking, well, we did the first infusion in the doctor’s office and we’ll do the rest at home. No, because we’ve seen patients do fine with the first 3, and then with the fourth or fifth they have a serious reaction,” Atkins said.

She said that administering therapies at home also deprives patients of important benefits, such as the presence of a physician they can ask about treatment issues and the camaraderie of fellow patients.

“There are many patients who don’t go anywhere, especially during the pandemic. The only place they get to go is my office. They come here and they see the same people. It’s like their chemo club, their community. They talk to each other and also support each other. When you have chemotherapy in the home, it actually just isolates the patient even more, because many patients with cancer feel extremely isolated,” Atkins said.

“Home infusion has inherent limitations in the level of care that can be provided and emergency interventions available to the individuals who are overseeing it,” COA stated. “Even when specifying that the administration of drugs would be by a professional specifically trained to administer these therapies, such individuals could not ensure patient safety without the backup of a team and necessary equipment and supportive drugs.”¹

Handley contends that the safety issue is overblown. Life-threatening reactions during home infusion are rare and usually occur in the first 30 minutes when a nurse is present, he said. Robust technologies are available to remotely monitor patients and enable quick responses to problems. He argued that existing Hospital at Home programs show that safety concerns are solvable and that the objections actually mask financial concerns or a fear of the unknown.

Questions Over Costs

Although data show that home infusion of therapies for various medical conditions is usually less costly than treatment in a hospital or clinic, Atkins said she believes that paying a specialized oncology nurse to care for 1 patient at a time raises costs and makes reimbursement difficult.

“I know UPenn has a deep pockets. They could probably do whatever they want to do. But in reality patients have Medicare, possibly Medicaid, and some private insur-ance. [Those payers] are not going to want to pay for a certified nurse. Chemo nurses are not inexpensive. To have 1 nurse sit with a patient for 5 or 6 hours—because some drugs take that long—is a waste of resources,” she said.

The financial implications of converting patients to in-home chemotherapy infusion are complex and can vary depending on several factors.

Handley said home infusion is less expensive than on-site administration when the fixed costs of operating an infusion clinic are included in the calculations. In addition, a well-developed, moderate-volume home-based system allows agile adjustment of nurse staff-ing that boosts efficiency and keeps labor costs down, he said. At the same time, some payers provide lower reimbursements for in-home care, which results in less health care spending overall but can create financial difficulties for providers.

“Lower costs may mean lower reimbursement, and the delta between how much things cost and how much you get paid is not always favorable. That’s the tricky situation we talk about,” Handley said.

A concern among independent practices is that the movement toward more home infusion threatens not only to cut into their revenues but also to take away control over their patients’ care. For example, an insurer could mandate home chemotherapy to cut costs and require members to use medication and nurses from its own specialty pharmacy, COA executive director Ted Okon said.

“You could see them saying, first of all, here’s the restricted formulary or step therapy, and we have to administer the drug to the patient in their home,” he said. “You’ve got the insurer/specialty pharmacy making the decision on the drug—not only who’s going to administer it but how it’s going to be administered and where. That’s a very, very scary thought.”

Sullivan said she was “a little bit perplexed” by the intense opposition to home infusion from some oncologists, adding that she believes business concerns are driving some of the objections. The infusion providers she represents are not clamoring to take over chemotherapy administration from practices, she said, but they do have many of years of training and experience in administering drugs to patients with cancer, including some chemotherapies, and they are well qualified to safely give a range of therapies if asked.

The 21st Century Cures Act of 2016 added a new home infusion services benefit to Medicare Part B, but CMS has interpreted the benefit as requiring a nurse to be physically present in the patient’s home in order for providers to be reimbursed.²⁴

NHIA says because the interpretation does not account for remote services, provider participation in the Medicare benefit has dropped over the past several years. The proposed Preserving Patient Access to Home Infusion Act would remove the physical presence requirement and require CMS to pay home infusion providers for each day drugs are administered.

However, the Medicare Part B benefit focus on drugs delivered through pumps and covers only 8 cancer drugs.²⁵ Handley said the legislative proposals he has seen would not have a major impact on in-home chemo-therapy programs such as those at Penn and Jefferson.

References

1. American Society of Clinical Oncology position statement: home infusion of anticancer therapy. American Society of Clinical Oncology. June 23, 2020. Accessed September 24, 2021. https://www.asco.org/sites/new-www.asco.org/files/content-files/advocacy-and-policy/documents/2020_Home-Infusion-Position-Statement.pdf
2. COA’s position statement on home infusion. Community Oncology Alliance. April 9, 2020. Accessed September 24, 2021. https://communityoncology.org/coas-position-statement-on-home-infusion
3. Home infusion therapy market 2021 by product type (infusion pumps, intravenous sets, IV cannulas, needleless connectors, vein imaging devices), by application (anti-infective, hydration therapy, chemotherapy, enteral nutrition, parenteral nutrition, others ), forecast to 2027. Brandessence. April 2020. Accessed October 10, 2021. https://brandessenceresearch.com/healthcare/home-infusion-therapy-market-size
4. Home infusion therapy market size, share & trends analysis report by product (infusion pumps, needleless connectors), by application (anti-infective, chemotherapy), by region, and segment forecasts, 2021 - 2028. Grand View Research. February 5, 2021. Accessed October 10, 2021. https://www.grandviewresearch.com/industry-analysis/home-infusion-therapy-market
5. Sánchez-Félix M, Burke M, Chen HH, Patterson C, Mittal S. Predicting bioavailability of monoclonal antibodies after subcutaneous administration: open innovation challenge. Adv Drug Deliv Rev. 2020;167:66-77. doi:10.1016/j.addr.2020.05.009
6. Epstein RS. Payer perspectives on intravenous versus subcutaneous administration of drugs. Clinicoecon Outcomes Res. 2021;13:801-807. doi:10.2147/CEOR.S317687
7. Phesgo. Prescribing information. Genentech; 2020. Accessed October 10, 2021. https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/761170s000lbl.pdf
8. FDA approves breast cancer treatment that can be administered at home by health care professional. FDA. News release. June 29, 2020. Accessed October 10, 2021. https://www.fda.gov/news-events/press-announcements/fda-approves-breast-cancer-treatment-can-be-administered-home-health-care-professional
9. Hawasli RSD, Barton S, Nabhani-Gebara S. Ambulatory chemotherapy: past, present, and future. J Oncol Pharm Pract. 2021;27(4):962-973. doi:10.1177/1078155220985916
10. Lokich J. Infusional 5-FU: historical evolution, rationale, and clinical experience. Oncology (Williston Park). 1998;12(10 suppl 7):19-22.
11. Laughlin AI, Begley M, Delaney T, et al. Accelerating the delivery of cancer care at home during the Covid-19 pandemic. NEJM Catal Innov Care Deliv. Published online July 7, 2020. Accessed October 11, 2021. doi:10.1056/cat.20.0258
12. Fairview Health Services. As COVID-19 pandemic surges, cancer patients like Dean opt for at-home chemotherapy. December 11, 2020. Accessed September 24, 2021. https://www.fairview.org/Blog/as-covid-19-surges-cancer-patients-opt-for-at-home-care
13. Oncology Home Infusion Program. United Healthcare. October 9, 2020. Accessed September 24, 2021. https://www.uhcprovider.com/content/dam/provider/docs/public/commplan/fl/forms-references/FL-Oncology-FAQ.pdf
14. CVS Health collaborates with Cancer Treatment Centers of America to provide in-home chemotherapy. CVS Health. January 12, 2021. Accessed September 24, 2021. https://cvshealth.com/news-and-insights/press-releases/cvs-health-collaborates-with-cancer-treatment-centers-of-america
15. Select oncology medications are being added to the Site of Care management program. Aetna. June 2020. Accessed September 24, 2021. https://www.aetna.com/health-care-professionals/newsletters-news/office-link-updates-june-2020/pharmacy-updates-june-2020/oncology-medications-added-to-the-site-of-care-management-program.html
16. NCCN Best Practices Committee Infusion Efficiency Workgroup. Toolkit: providing oncology treatments in the outpatient setting. Revised March 31, 2020. Accessed October 11, 2021.
17. NCCN. The National Comprehensive Cancer Network infusion toolkit: reducing inefficiencies in chemotherapy in the US. Accessed October 11, 2021. https://www.all-can.org/efficiency-hub/the-national-comprehensive-cancer-network-infusion-toolkit-reducing-inefficiencies-in-chemotherapy-in-the-us/
18. Leff B, Burton L, Mader SL, et al. Hospital at home: feasibility and outcomes of a program to provide hospital-level care at home for acutely ill older patients. Ann Intern Med. 2005;143(11):798-808. doi:10.7326/0003-4819-143-11-200512060-00008
19. Leff B, Burton L, Mader S, et al. Satisfaction with hospital at home care. J Am Geriatr Soc. 2006;54(9):1355-1363. doi:10.1111/j.1532-5415.2006.00855.x
20. Lüthi F, Fucina N, Divorne N, et al. Home care - a safe and attractive alternative to inpatient administration of intensive chemotherapies. Support Care Cancer. 2012;20(3):575-581. doi:10.1007/s00520-011-1125-9
21. Brown DF, Muirhead MJ, Travis PM, Vire SR, Weller J, Hauer-Jensen M. Mode of chemotherapy does not affect complications with an implantable venous access device. Cancer. 1997;80(5):966-972. doi:10.1002/(sici)1097-0142(19970901)80:5<966::aid-cncr20>3.0.co;2-t
22. Beijer S, Gielisse EA, Hupperets PS, et al. Intravenous ATP infusions can be safely administered in the home setting: a study in pre-terminal cancer patients. Invest New Drugs. 2007;25(6):571-579. doi:10.1007/s10637-007-9076-1
23. Evans JM, Qiu M, MacKinnon M, Green E, Peterson K, Kaizer L. A multi-method review of home-based chemotherapy. Eur J Cancer Care. 2016;25(5):883-902. doi:10.1111/ecc.12408
24. NHIA applauds house introduction of bipartisan home infusion legislation. News release. National Home Infusion Association. August 23, 2021. Accessed October 11, 2021. https://nhia.org/nhia-applauds-house-introduction-of-bipartisan-home-infusion-legislation/
25. MLN Matters. Billing for home infusion therapy services on or after January 1, 2021. Centers for Medicare & Medicaid Services. December 31, 2020. Accessed October 11, 2021. https://www.cms.gov/files/document/mm11880.pdf