From Infusion to Injection: Can Subcutaneous Delivery Match Intravenous Standards in Oncology?

Subcutaneous (SC) formulations are redefining how monoclonal antibodies and immunotherapies are delivered in oncology. Traditionally administered intravenously (IV), agents such as trastuzumab, daratumumab, and nivolumab are now being studied—and in many cases, approved—for SC use. The clinical question is no longer whether this route is easier, but whether it is equivalent. Across multiple tumor types, the answer increasingly appears to be yes: SC delivery matches IV therapy in pharmacokinetics, efficacy, and safety.^1,2

Pharmacokinetics That Hold the Line

Non-inferiority trials have consistently confirmed that SC administration achieves drug exposure levels on par with IV infusion, meeting or exceeding prespecified pharmacokinetic (PK) targets:

• Daratumumab in multiple myeloma (COLUMBA): SC daratumumab achieved slightly higher trough serum concentrations than IV, supporting non-inferior exposure. Both arms showed similar median progression-free survival around five to six months. Median overall survival (OS) was also similar at about 26 months for the IV group compared to 28 months for the SC group and an overall response rate (ORR) of 40 percent versus 44 percent, respectively.³
• Atezolizumab in non-small cell lung cancer (IMscin001): Trough concentration after the first dose was approximately five percent higher with SC administration. Total exposure was within 87 percent of IV delivery, and ORR were similar at 12 percent for SC versus 10 percent for patients administered IV.⁴ In an updated analysis with mature OS data, median OS was also similar between treatment arms at 10.7 versus 10.1 months in the subcutaneous and intravenous groups, respectively.⁵
• Nivolumab in renal cell carcinoma (CheckMate-67T): The SC co-formulation with hyaluronidase also demonstrated equivalent PK and an even higher objective response rate—24 percent in SC versus 18 percent in IV treatment arms. Based on these data, the FDA approved SC nivolumab for most of its IV indications.⁶
• Pertuzumab + trastuzumab in HER2-positive breast cancer (FeDeriCa): Trough pertuzumab concentrations at cycle eight were 22 percent higher with SC administration (93.7 micrograms per milliliter versus 78.5 micrograms per milliliter), with equivalent pathologic complete response rates of approximately 60 percent.⁷

A Trade-Off in Safety

Across trials, SC formulations have shown no increase in systemic toxicity and no new safety concerns. Overall adverse event rates, including grade three or higher events, have been consistently on par with IV administration.

However, a main difference with IV therapies is that SC administration is associated with a higher incidence of injection site reactions, which are most often mild and treatable, in conjunction with a reduced rate of infusion-related reactions.^1,2

• Infusion-related reactions, which are common with IV monoclonal antibodies, are generally reduced with SC dosing. In COLUMBA, infusion-type reactions occurred in 13 percent of patients receiving SC daratumumab compared to 34 percent in the IV group.³ This may reflect more stable serum drug levels with SC administration, which avoids the sharp peaks associated with IV infusion.
• On the other hand, injection site reactions are more commonly seen with SC administration but remain manageable. In trials of SC rituximab, for example, erythema or swelling occurred in about half of patients, while severe local reactions were rare (approximately two percent) and typically transient. Discontinuation due to local reactions has been exceedingly rare across studies.⁸

Moving Ahead Without Compromise

The oncology landscape is increasingly shifting toward SC administration—not as a shortcut, but as a thoughtful evolution in care without compromising PK, efficacy, or safety. Evidence from this expanded treatment landscape also demonstrate gains in tolerability, reduced healthcare resource utilization, and expense, as well as strong patient and provider preference for this route of administration. SC regimens are reshaping how cancer therapies are delivered where the goal is not only to help patients live longer, but also to improve how they live.^1,2

References:

1. George S, Bourlon MT, Overman MJ, et al. Systematic literature review of intravenous versus subcutaneous administration of oncology therapies: a clinical, economic and patient perspective. Cancer Treat Rev. 2025;139:102974. doi:10.1016/j.ctrv.2025.102974
2. Davis JD, Bravo Padros M, Conrado DJ, et al. Subcutaneous administration of monoclonal antibodies: pharmacology, delivery, immunogenicity, and learnings from applications to clinical development. Clinical Pharmacology & Therapeutics. 2024;115(3):422–439. doi:10.1002/cpt.3150
3. Usmani SZ, Nahi H, Legiec W, et al. Final analysis of the phase III non-inferiority COLUMBA study of subcutaneous versus intravenous daratumumab in patients with relapsed or refractory multiple myeloma. Haematologica. 2022;107(10):2408–2417. doi:10.3324/haematol.2021.279459
4. Burotto M, Zvirbule Z, Mochalova A, et al. IMscin001 Part 2: a randomised phase III, open-label, multicentre study examining the pharmacokinetics, efficacy, immunogenicity, and safety of atezolizumab subcutaneous versus intravenous administration in previously treated locally advanced or metastatic non-small-cell lung cancer and pharmacokinetics comparison with other approved indications. Ann Oncol. 2023;34(8):693–702. doi:10.1016/j.annonc.2023.05.009
5. Burotto M, Zvirbule Z, Alvarez R, et al. Brief report: updated data from IMscin001 Part 2, a randomized phase III study of subcutaneous versus intravenous atezolizumab in patients with locally advanced or metastatic NSCLC. J Thorac Oncol. 2024;19(10):1460–1466. doi:10.1016/j.jtho.2024.05.005
6. Albiges L, Bourlon MT, Chacon M, et al. Subcutaneous versus intravenous nivolumab for renal cell carcinoma. Ann Oncol. 2025;36(1):99–107. doi:10.1016/j.annonc.2024.09.002
7. Tan AR, Im SA, Mattar A, et al. Fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection plus chemotherapy in HER2-positive early breast cancer (FeDeriCa): a randomised, open-label, multicentre, non-inferiority, phase 3 study. Lancet Oncol. 2021;22(1):85–97. doi:10.1016/S1470-2045(20)30536-2
8. García‐Muñoz R, Quero C, Pérez‐Persona E, et al. Safety of switching from intravenous to subcutaneous rituximab during first‐line treatment of patients with non‐Hodgkin lymphoma: the Spanish population of the MabRella study. British Journal of Haematology. 2020;188(5):661–673. doi:10.1111/bjh.16227