With Sub-Q Immunotherapy Coming, “Patient Preference Has to Be the Key”

The recent approval of subcutaneous nivolumab injection (Opdivo Qvantig) marks the next step in the evolution of cancer therapy—and one that promises new solutions for patients and cancer centers alike, according to an oncologist who spoke at the Association for Cancer Care Centers’ 51st Annual Meeting & Cancer Center Business Summit.

Raghava Reddy Induru, MD | Image: Atrium Health

Raghava Reddy Induru, MD, who is based in Albemarle, North Carolina, for Atrium Health Levine Cancer Institute, walked attendees through the trajectory of the “pillars” of cancer treatment, from the surgery practiced by the ancient Greeks to the discovery of radiation in the 1800s, to the rise of chemotherapy and targeted therapies in the last century. More recently, the field has seen the approval of the first immunotherapies, coupled with the shift to genomic-based treatment.

But new treatments are only part of the story, Induru said. “Evolution comes from many, many different angles, and part of the evolution is how we administer these medications.”

In the 1940s, the launch of chemotherapy came with intravenous (IV) administration. “It’s considered the gold standard…because it’s predicable. We understand the bioavailability very easily,” he said.

Oral medications arrived in the mid-1990s. Induru said at first, there were challenges because the bioavailability compared with IV administration was not well understood, "but we have made the transition.”

More recently, hematology and oncology have embraced subcutaneous delivery, in which therapy is delivered directly under the skin; this method allows rapid delivery of the medication relative to the time needed for IV administration. Induru cited data that showed average savings of 54 minutes per patient, although the time saved has varied by country.

Subcutaneous delivery has been used for some time, including for well-known therapies such as trastuzumab (Herceptin), which is used in HER2-positive breast cancer, and bortezomib (Velcade), and daratumuab (Darzalex), both used in multiple myeloma. However, FDA's December 27, 2024, approval of a subcutaneous formulation of nivolumab across multiple solid tumors marks the first time a checkpoint inhibitor will be delivered this way, which Induru said is a significant step.

Although J-codes are not yet available, he said, they are coming soon, and subcutaneous versions of other immune checkpoint inhibitors will follow. He predicts health systems will see clinical and operational benefits, and patients will benefit, too.

“This is unstoppable,” he said. “But how we embrace this is really [what] we need to think of.”

Induru shared a few case studies of patients for whom a subcutaneous option offered benefits. A 54-year-old woman with HER2-postive progressive breast cancer would need a multidisciplinary regimen—she had adjuvant therapy with trastuzumab and pertuzumab for 4 cycles; she experienced neutropenic fever and had COVID prior to surgery, which complicated her care. However, she had a complete pathological response. What would come next? Standard of care would be trastuzumab and pertuzumab for 4 months, but this patient no longer had a port.

“A good clinical trial is always the best option for my patients, right?” Induru said. The clinical trial options were IV trastuzumab vs subcutaneous trastuzumab; the trial called for a longer duration of treatment, and IV would be a challenge for a year. “Subcutaneous would be a great option,” he said, but it is “confounded with the whole challenge of getting approval.”

Another case involved a 48-year-old man with symptomatic multiple myeloma who runs his own trucking company. The patient has 5 children; he declined the port and wanted early morning or late day appointments because of his work schedule.

This story reflects what Induru sees in the rural area he serves. His patient "can’t just stop working, because he’s paid for his own self-insurance. These are very critical components of his life. He is a young male supporting his family…. What are his choices?”

Induru ran through various well-known triplets and quadruplets approved in recent years for multiple myeloma. After noting that the regimen of daratumumab, bortezomib, lenalidomide and dexamethasone can given with a mix of subcutaneous and oral options, he added, “I don’t have an answer, but [I’m] just helping people to think about who my patient is, and what is the right choice for them.”

Considerations for Bringing Subcutaneous Drugs Into Practice

Practical considerations for health systems including whether clinical trials comparing IV and subcutaneous formulations have been completed and how costs compare, Induru said. At this point, most studies are designed to show noninferiority with IV formulations, he said. (The Checkmate-67T study involving 495 patients met the pharmacokinetic, overall response rate, and safety end points.)

Savings, he explained, cannot be evaluated simply within the comparison of therapies themselves. The large reduction in time of administration will make scheduling easier, and may allow a complete rethinking of workforce optimization.

“It reduces the hospital and clinic burden—no question about it,” he said. In the area where subcutaneous therapy is given, “The way we staff that is different, and how we look at the utilization of the time is different than what we're doing with the infusion [area].”

If more patients can be treated with subcutaneous therapy, “I may have more people now who could make sure that the patients are coming for their appointments, or [staff] who could use the time to coordinate these appointments,” Induru said. With help from AI, “That’s how I [will] better use my resources.”

The most important consideration, he said, is what the patient wants, and with the arrival of the subcutaneous option, home administration of therapy is not out of the question. Although IV administration still has some advantages, “Patient preference has to be the key,” Induru said.