Addressing the Logistics of At-Home Cancer Care With Subcutaneous Administration of Immunotherapy

Jorge J. Nieva, MD

As telehealth is now routinely offered in health care, determining how at-home care fits into oncologic care is top of mind, with the subcutaneous formulation of agents serving as a more feasible administration pathway as opposed to that of intravenous (IV) therapy. As such, investigators have initiated a first-of-its-kind clinical trial where patients with non–small cell lung cancer (NSCLC) will receive subcutaneous immunotherapy in the comfort of their own homes.¹

“The loosening of regulations around payments for telemedicine have done wonders for the field. Before, patients had to do the telemedicine visits at their rural critical access hospitals—they weren’t able to be at home. Being able to use consumer platform technologies does simplify the process. There’s no need for special equipment or unusual technological requirements as we had before the COVID-19 pandemic,” Jorge J. Nieva, MD, a medical oncologist at Keck Medicine of University of Southern California (USC) and an associate professor of clinical medicine at Keck School of Medicine in Los Angeles, explained in an interview with OncologyLive.

Currently indicated for IV use in the US, atezolizumab (Tecentriq) is being evaluated in a subcutaneous delivery route to allow for safe and effective administration by a nurse to patients at home in a phase 2 study (NCT05340309) conducted by USC/Norris Comprehensive Cancer Center.^1,2 Telemedicine appointments and remote monitoring through wearable trackers are additional components of the study. Nieva, who is the lead investigator of the clinical trial, added that telemedicine has come a long way from its inception.

“I have been around telemedicine for a long time,” Nieva noted. “I spent approximately 7 years practicing medicine in Montana, and we did a lot of telemedicine long before the COVID-19 [pandemic]. It was an essential aspect of care for patients who lived in rural environments near critical access hospitals.”

He added, “What makes this clinical trial unique is it’s the first home administration of immunotherapy for solid tumors and it’s [a trial] where we’re leveraging consumer-grade technologies for fitness monitoring and using them for performance status assessments. We’ve also built a network for getting laboratory studies into our electronic medical record through our partnerships with third-party laboratory vendors such as Labcorp and Quest Diagnostics. We try to ensure that CT monitoring is done in ways where we can view the images and deliver the results to the patients through telemedicine.”

The Subcutaneous Route Allows for Flexibility and Cost Savings Over the IV Route

As oral medicines become more common, particularly for patients with actionable driver mutations, Nieva noted that agents given via the subcutaneous route are growing in scope as well due to the ease they provide with administration.

“In this clinical trial, we ensure safety by [administering] the first 3 infusions in the office to be sure that there aren’t going to be problems with allergic reactions. This medicine, [atezolizumab], is a monoclonal antibody, and there is a long experience with biological agents and monoclonal antibodies being delivered at home through subcutaneous infusions. Gamma globulin is one example; recombinant factors for people with hemophilia is another. There isn’t a priori reason that monoclonal antibodies could not be delivered at home through subcutaneous routes,” Nieva said.

In most recent subcutaneous news, the FDA accepted a biologics license application in May 2024 for the subcutaneous formulation of nivolumab (Opdivo) coformulated with Halozyme’s proprietary recombinant human hyaluronidase (rHuPH20) for the treatment of adult patients who are eligible for prior solid tumor nivolumab indications; this includes monotherapy, monotherapy maintenance following completion of nivolumab plusipilimumab (Yervoy), or in combination with chemotherapy or cabozantinib (Cabometyx).³

Findings from a study also revealed that cost savings with subcutaneous formulations of agents could be large; a model developed to estimate cost differences for transitioning 20% of a patient cohort from IV to subcutaneous rituximab (Rituxan) found that in a plan of 1 million individuals this could save $153,000 in total from a payer perspective. From a practice perspective, $124,000 could be saved, and provider capacity could be increased by 270 hours of staff time. The model found that in addition to potentially generating significant US health system value via payer savings, increased practice capacity and patient time would generate value.⁴

The 20% transition in the model from IV to subcutaneous formulation was projected to save approximately 470 hours of patient time as well. When examined by tumor type, patients with diffuse large B-cell lymphoma and follicular lymphoma were found to have an estimated IV infusion duration of 234 minutes and for chronic lymphocytic leukemia, the duration is estimated at 273 minutes; overall, subcutaneous administration is estimated at 60 minutes across all service levels.

In addition to cost savings as a reason to consider subcutaneous administration, including in cases where this care can be given at home, countries outside the US have administered subcutaneous agents at a higher rate. A retrospective cross-sectional study examining treatment in the US vs Canada noted that subcutaneous and IV drugs are coded, managed, and billed differently in the US. The study included data from the acute palliative care units of The University of Texas MD Anderson Cancer Center in Houston and Princess Margaret Cancer Centre in Toronto, Ontario—centers that practice care for patients with cancer at the end of life similarly.⁵

When examining administration, data revealed that of patients receiving care in Canada (n = 191) vs the US (n = 198), patients received subcutaneous agents only (55.5% vs 0.0%), IV only (4.7% vs 99.5%), and both (39.8% vs 0.5%), respectively.

Turning to the Logistics: Administration and Assessment of Performance Status

When examining the subcutaneous route with at-home administration and telemedicine visits that will take place, Nieva noted that data from wearable fitness monitors and smartphones can be a way to gather fitness information on patients. He added, “Using as many tools at your disposal to try to get an accurate assessment of your patients’ performance status is going to be important, and I believe it can be done by telemedicine. Trying to leverage some other orthogonal information that informs patient performance is a key feature of providing good telemedicine visits for your patients.”

“The biggest problem with telemedicine is it’s very hard to assess performance status and functionality of the patients because you don’t get to see the patient move in telemedicine as cameras tend to be fixed,” Nieva said. “In this clinical trial, we have a dashboard that gives us patient-derived information such as vital signs, weight, results from patient-reported outcome survey questionnaires, and other metrics of health and well-being that we can look at to provide optimal care for patients. That’s something that we’ve custom designed for this clinical trial. [For] other telemedicine appointments, I don’t currently have that dashboard created, so we have to do more in terms of questioning patients [and] sometimes doing things such as asking the camera to be repositioned and having the patient get up and walk around a little bit in the room while I watch them walk.”

In addition to keeping a close eye on assessing performance status during telemedicine visits, a key component of the trial will include the nurses administering the subcutaneous atezolizumab to patients. Nieva noted that currently USC has contracted with Mobile Medical LA, which provides at home nursing services across a broad range of indications. The nurses will travel throughout Southern California to deliver atezolizumab to patients.

“They’re not specifically research nurses, but they follow the research protocol in terms of delivering the medications. The key logistics, and probably the most important logistical challenges, are making sure that the medicine is shipped to the patient’s home and that it’s shipped cool,” Nieva noted. “We have the nurse open the shipping container rather than the patient to ensure that there’s no temperature variance that would lead to instability of the product. That works out well, but it does require a bit of coordination on our end and [for] our pharmacy to go from the order [of] administering the medicine after the results of laboratory studies are obtained to having the medicine shipped to the patient’s home, and then coordinating that with the arrival of the nurse.”

Delving Into the Next Steps With Telemedicine

Furthermore, the National Cancer Institute Telehealth Research Centers of Excellence (TRACE) is funding multiple centers focused on improving lives. Ways the centers are taking action include developing evidence-based telehealth approaches across cancer care, and evaluating the changing policy and payment environment as well as its impact on delivery of telehealth for cancer care, among others. The University of Pennsylvania TRACE is 1 of 4 TRACE centers, and it uses lung cancer care as a model for telehealth across the care continuum.⁶

As telemedicine and subcutaneous delivery of agents continues to expand, the at-home study conducted by USC remains open to enrollment for patients with NSCLC. Patients will receive atezolizumab and rHuPH20 subcutaneously for 3 to 8 minutes on day 1 with cycles repeating every 3 weeks for 1 year for those with early-stage disease or up to 2 years for those with late-stage disease until disease progression or unacceptable toxicity.⁷

“Patients who have high copays or who have difficulty with health maintenance organization coverage of these checkpoint inhibitors for lung cancer [treatment] are welcome to contact us, and we’d be happy to determine if they are eligible for clinical trial participation,” Nieva said.

References

1. Study explores the future of at-home cancer treatment. News release. Keck Medicine of USC. March 28, 2024. Accessed
   May 8, 2024. bit.ly/3wrUv6q
2. Tecentriq. Prescribing information. Genentech Inc; 2024.
   Accessed May 8, 2024. bit.ly/3ycReZr
3. US Food and Drug Administration accepts Bristol Myers Squibb’s application for subcutaneous nivolumab (nivolumab and
   hyaluronidase). News release. Bristol Myers Squibb. May 6, 2024. Accessed May 8, 2024. bit.ly/4dyDtUO
4. Harvey MJ, Zhong Y, Morris E, Beverage JN, Epstein RS, Chawla AJ. Assessing the transition from intravenous to subcutaneous delivery of rituximab: benefits for payers, health care professionals, and patients with lymphoma. PLoS One. 2022;17(1):e0261336. doi:10.1371/journal.pone.0261336
5. Tang M, Abdelaal M, Lau J, et al. Subcutaneous vs intravenous administration of medications and fluids for patients with cancer in the US and Canada. JAMA Oncol. 2023;9(5):717-719. doi:10.1001/jamaoncol.2023.0239
6. TRACE overview. NCI Telehealth Research Centers of Excellence (TRACE). Accessed May 8, 2024. bit.ly/3JW66Op
7. Subcutaneous atezolizumab for the treatment of non-small cell lung cancer. ClinicalTrials.gov. Updated February 13, 2024. Accessed May 8, 2024. https://classic.clinicaltrials.gov/ct2/show/NCT05340309