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Nivolumab has been approved for subcutaneous use across several adult solid tumor indications that have an existing indication for intravenous use.
Subcutaneous Nivolumab in Solid Tumors
| Image Credit: © Katsyarina – stock.adobe.com
Subcutaneous nivolumab (Opdivo) co-formulated with recombinant human hyaluronidase has been approved by both Health Canada and the European Commission (EC) for use in adults with solid tumors as monotherapy, monotherapy maintenance following completion of intravenous (IV) nivolumab plus ipilimumab (Yervoy) combination therapy, or in combination with chemotherapy or TKIs such as cabozantinib (Cabometyx).1,2
The new subcutaneous solution for injection is given every 2, 3, or 4 weeks and should not be used simultaneously with ipilimumab.1 The European Commission also approved a new strength of 600 mg/vial.2
“The burden of traveling long distances for care can be significant, particularly for individuals living in northern or rural communities,” Dr Silvana Spadafora, medical oncologist at Sault Area Hospital in Sault Ste. Marie Ontario, Canada, stated in a news release.1 “Having a subcutaneous option of [nivolumab] offers patients and their care teams a potentially more flexible treatment approach that may support more equitable access to care.”
Both approvals are based in part on data from the phase 3 CheckMate 67T trial (NCT04810078), which showed that subcutaneous administration was noninferior to intravenous (IV) administration with respect to pharmacokinetics and efficacy.1,2
CheckMate 67T was a randomized, open-label, noninferiority trial evaluating subcutaneous nivolumab vs IV nivolumab in adult patients with advanced or metastatic, immunotherapy-naive clear cell renal cell carcinoma who received 1 or 2 lines of prior systemic therapy.3,4 A total of 495 patients were randomly assigned to receive 1200 mg of subcutaneous nivolumab every 4 weeks (n = 248) or 3 mg/kg of IV nivolumab every 2 weeks (n = 247). Treatment was continued for 2 years, or until disease progression, unacceptable toxicity, consent withdrawal, or death.
The coprimary end points were time-averaged concentration over 28 days (Cavgd28) and minimum concentration at steady state (Cminss). The key powered secondary end point was overall response rate (ORR) as assessed by blinded independent central review.
The geometric mean ratio (GMR) for Cavgd28 was 2.098 (90% CI, 2.001-2.200) and the GMR for Cminss was 1.774 (90% CI, 1.633-1.927). Additionally, the ORR in the subcutaneous arm was 24.2% (95% CI, 19.0%-30.0%) compared with 18.2% (95% CI, 13.6%-23.6%) in the IV arm.
Findings from the study also supported the earlier December 2024 FDA approval of the regimen in the US.5
“This approval represents a meaningful advancement for patients with solid tumors and the teams that care for them,” Sebastien Hotte, MD, MSc (HRM), FRCPC, medical oncologist at the Juravinski Cancer Centre in Kingston, Ontario, Canada, said in a news release.1 “Subcutaneous delivery of nivolumab has the potential to help reduce pressure on clinic resources and streamline workflows, offer added convenience to patients, and facilitate administration of immunotherapy, especially in the maintenance phase of treatment plans.”
Additional findings from the trial, which were presented at the 2024 Genitourinary Cancers Symposium and published in the Annals of Oncology revealed that the median disease control rate was 62.5% (95% CI, 56.2%-68.5%) with the subcutaneous formulation vs 62.8% (95% CI, 56.4%-68.8%) with the IV formulation (risk ratio, 1.00; 95% CI, 0.88-1.15).3,4 The median time to response was 3.71 months (range, 1.7-11.3) and 3.68 months (range, 1.6-13.8) in the subcutaneous and IV arms, respectively. The median progression-free survival was 6.34 months (95% CI, 5.13-7.49) and 5.65 months (95% CI, 5.29-7.39), respectively (HR, 1.06; 95% CI, 0.85-1.32).
“From redefining the oncology landscape with the first immunotherapy approvals over a decade ago to today’s advancement, Bristol Myers Squibb is proud to continue pushing the boundaries of what’s possible in cancer care,” Elaine Phillips, general manager, Bristol Myers Squibb Canada, said.1 “[Subcutaneous nivolumab] builds on the clinical experience with IV nivolumab, offering a new approach to treatment delivery that reflects our ongoing commitment to evolving care and supporting the needs of patients and providers alike.”
The safety profile between the two formulations was similar. 3,4 Any-grade treatment-related adverse effects (TRAEs) occurred in 61.5% of patients in the subcutaneous arm (grade 3/4, 11.7%) vs 65.7% of those in the IV arm (grade 3/4, 17.1%). TRAEs leading to discontinuation occurred in both the subcutaneous (any grade, 4.5%; grade 3/4, 2.8%) and IV (any grade, 5.3%; grade 3/4, 3.7%) arms. Select AEs were hypersensitivity/infusion-related reactions and local site reactions, which occurred in the subcutaneous arm in 0.4% (grade 3/4, 0.4%) and 7.3% (grade 3/4, 0%) of cases, respectively, vs 2.9% (grade 3/4, 0%) and 2.0% (grade 3/4, 0%) of cases in the IV arm.
“The EC’s decision to approve [subcutaneous nivolumab] ushers in a new era of cancer care in which we are able to deliver a 3- to 5-minute injection of a treatment that has shown consistent efficacy and comparable safety to IV [nivolumab], which changed the cancer treatment landscape over a decade ago,” Dana Walker, MD, MSCE, Opdivo global program lead, Bristol Myers Squibb, stated in a news release.2 “Bristol Myers Squibb is committed to advancing medicines that help improve the patient experience, and with the approval of [subcutaneous nivolumab] in the European Union, we are delivering on this goal.”
The most common any-grade AEs that occurred in the subcutaneous and IV arms, respectively, were arthralgia (11.7% vs 15.9%), fatigue (7.7% vs 15.9%), diarrhea (9.7% vs 13.5%), hyperglycemia (9.3% vs 13.1%), decreased appetite (8.9% vs 11.4%), back pain (7.7% vs 11.0%), peripheral edema (4.5% vs 9.8%), nausea (8.1% vs 9.0%), hypokalemia (6.9% vs 8.6%), and abdominal pain (6.5% vs 6.5%),3 mirroring the most common AEs reported with IV nivolumab from a pooled dataset across tumor types (n = 4,646): fatigue (44%), musculoskeletal pain (28%) and diarrhea (26%).1
“As the first and only subcutaneously administered PD-1 inhibitor approved in the European Union, subcutaneous nivolumab is helping to transform the treatment landscape for eligible patients by giving them a new way to potentially receive the same benefits of the IV formulation of nivolumab, in a more convenient manner,” Laurence Albiges, MD, PhD, a professor of medical oncology at Université Paris-Saclay, and head of the Department of Oncology at Gustave Roussy, Villejuif, France, added in a news release.“This approval provides eligible patients and their doctors a new way to tailor treatment plans for each individual’s needs and to improve the efficiency with which nivolumab can be administered from a patient perspective as well as in the organization of our health care resources.”
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