Subcutaneous Pembrolizumab Faces Scrutiny Over Convenience and Cost for Patients With Cancer

Author(s)Kyle Doherty

Fact checked by: Chris Ryan

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Key Takeaways

FDA approval relied on PK endpoints (cycle 1 AUC0–6 weeks and cycle 3 Ctrough), not demonstrable improvements in patient experience, clinical efficacy, or treatment burden versus IV pembrolizumab.
Trial MK-3475A-D77 in treatment-naive metastatic NSCLC showed higher pembrolizumab exposure with subcutaneous dosing and similar ORR and safety, supporting PK noninferiority comparability.
Convenience gains may be overstated because room-temperature equilibration, travel, and standard infusion-center workflows persist, blunting net reductions in total visit time.
Market-exclusivity extension via reformulation could preempt IV biosimilar penetration after 2028 (US) and 2031 (EU), prolonging higher spend without clear incremental benefit.
Fixed 395/790 mg subcutaneous dosing limits flexibility relative to IV strategies, potentially undermining dose-optimization efforts and access expansion, particularly in low- and middle-income settings.

Laure-Anne Teuwen, MD, PhD, debates the real-world advantages of subcutaneous pembrolizumab.

Although pembrolizumab and berahyaluronidase alfa-pmph (subcutaneous pembrolizumab; Keytruda Qlex) has been heralded as an innovation for patients that promises shorter administration times and improved comfort compared with intravenous (IV) administration, questions remain surrounding the cost and potential clinical implications of this advancement, according to Laure-Anne Teuwen, MD, PhD.¹

“The subcutaneous version of pembrolizumab is being promoted as more convenient for patients,” Teuwen said in a statement to OncLive®. “We question this assumption and argue that this reformulation is primarily a strategy to delay biosimilar competition and prolong market exclusivity. The key question is whether subcutaneous pembrolizumab is actually more convenient for patients than IV pembrolizumab. At first sight, it appears to save time. The subcutaneous injection takes 1 minute for the 3-week dose and 2 minutes for the 6-week [dose], vs 30 minutes for the IV formulation. Yet, the subcutaneous drug must first reach room temperature for at least 30 minutes, and patients still need to travel to the cancer center to complete the usual treatment visit. Overall, the convenience advantage [can be] dubious.”

Teuwen is a medical oncologist at University Hospital of Antwerp in Edegem, Belgium.

What data supported the FDA approval of subcutaneous pembrolizumab?

In September 2025, the FDA approved subcutaneous pembrolizumab for adult and pediatric patients 12 years of age and older for solid tumor indications approved for the intravenous formulation of pembrolizumab.² The approval was supported by data from the phase 3 Study MK-3475A-D77 (NCT05722015), which evaluated the pharmacokinetics and safety of subcutaneous pembrolizumab coformulated with hyaluronidase vs IV pembrolizumab in patients with treatment-naive metastatic non–small cell lung cancer, without EGFR, ALK, or ROS1 aberrations.^2,3 The dual primary end points were cycle 1 AUC_{0-6 weeks}and cycle 3 C_trough.

Study MK-3475A-D77 randomly assigned patients 2:1 to receive subcutaneous pembrolizumab (n = 251) or IV pembrolizumab (n = 126); both arms were treated every 6 weeks in combination with platinum-doublet chemotherapy.³ At a median follow-up of 9.6 months (range, 6.24-16.39), findings from the trial revealed that the geometric mean ratio (GMR) for cycle 1 AUC_{0-6 weeks}was 1.14 (96% CI, 1.06-1.22; P < .0001). The GMR for steady-state C_trough was 1.67 (94% CI, 1.52-1.84); P < .0001). The secondary pharmacokinetic end points were found to be within the established bounds for IV pembrolizumab.

The overall response rates (ORRs) in the investigational and control arms were 45.4% (95% CI, 39.1%-51.8%) and 42.1% (95% CI, 33.3%-51.2%), respectively (odds ratio, 1.08, 95% CI 0.85-1.37). The study authors underscored that additional efficacy measures and the safety profiles were consistent between the 2 arms.

“The approval for the subcutaneous formulation was based on pharmacokinetic noninferiority, rather than evidence of improved patient experience,” Teuwen contended.

Does subcutaneous pembrolizumab offer advantages over the IV formulation?

In an article published in the Journal of Clinical Oncology, Teuwan and coauthors sought to examine the value that subcutaneous pembrolizumab adds for patients and health systems.¹ They argued that although the subcutaneous formulation offers practical advantages over IV administration, evidence that it improves patient experience or efficacy remains limited. The study authors also emphasized that the timing of the arrival of subcutaneous pembrolizumab is closely aligned with upcoming patent expiry and new pricing regulations.

Unpacking the Role of Subcutaneous Pembrolizumab

Subcutaneous pembrolizumab gained FDA approval based on pharmacokinetic noninferiority with comparable response rates and safety with the IV formulation.

Laure-Anne Teuwen, MD, PhD, argues that the convenience advantage of subcutaneous pembrolizumab is overstated, noting that required preparation time, travel, and routine clinic visits minimize meaningful time savings for patients.

Teuwen and colleagues caution that widespread adoption of the subcutaneous formulation could delay uptake of lower-cost IV biosimilars, increase health care spending, and limit dose-flexibility strategies without providing clear clinical or patient-centered benefits.

“The subcutaneous formulation extends market exclusivity for the manufacturer, a strategy known as ‘patent hopping’,” Teuwen said. “The patents for IV pembrolizumab expire in 2028 in the United States and in 2031 in Europe, after which lower-cost IV biosimilars [may] become available. If patients are switched to the patented subcutaneous formulation before then, the market for IV biosimilars will shrink, and health systems will continue paying high prices instead of benefiting from cheaper biosimilars. In the absence of a clear patient benefit, health systems should be encouraged to continue using the IV formulation.”

Teuwen and her coauthors explained that following the launch of trastuzumab and hyaluronidase (subcutaneous trastuzumab; Herceptin Hylecta), centers in The Netherlands adopted the formulation heterogeneously, with some fully transitioning to subcutaneous administration and others maintaining use of the IV formulation to allow for a future transition to biosimilars. Findings from a study published in The European Journal of Health Economics revealed that switching decisions were mostly unrelated to patient preferences and were informed by logistical considerations, supply contracts, or insurer-specific reimbursement policies.⁴

Additionally, although the subcutaneous formulation reduced administration time, the overall cost of the drug increased. Trastuzumab was estimated to have increased total medicine expenditures by approximately 5% compared with all of the centers fully transitioning to biosimilars.

“The actual time savings are modest when the entire treatment visit is considered,” Teuwen added. “More importantly, switching patients to a patented subcutaneous formulation limits future savings from IV biosimilars. This increases cost without necessarily improving patient outcomes.”

Teuwen and her coauthors also noted that practical factors often mitigate potential advantages of subcutaneous pembrolizumab in terms of convenience for patients and efficiency for health care systems. “[An] important limitation is dose flexibility. Subcutaneous pembrolizumab uses fixed doses of 395 mg or 790 mg, while IV pembrolizumab allows weight-based and lower-dose strategies. As studies worldwide are showing that lower doses of immunotherapy may be sufficient, implementation of the subcutaneous formulation would directly impede efforts to reduce drug use and expand access, particularly in low- and middle-income countries,” she said.

“Subcutaneous formulations change how drugs are administered, but this should not be confused with [necessarily] improving cancer care,” Teuwen concluded. “Future research should demonstrate benefits for patients and health systems, including reduced treatment burden, lower costs, greater dose flexibility, and improved access. Reformulations should not be adopted just because they are new or marketed as convenient.”

References

Teuwen LA, Riechelmann RP, Gyawali B. Beyond convenience: does subcutaneous pembrolizumab add value for patients and health systems? J Clin Oncol. 2026;44(20):1860-1864. doi:10.1200/JCO-25-02619
FDA approves pembrolizumab and berahyaluronidase alfa-pmph for subcutaneous injection. FDA. September 19, 2025. Accessed July 16, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pembrolizumab-and-berahyaluronidase-alfa-pmph-subcutaneous-injection
Felip E, Rojas CI, Schenker M, et al. Subcutaneous versus intravenous pembrolizumab, in combination with chemotherapy, for treatment of metastatic non-small-cell lung cancer: the phase III 3475A-D77 trial. Ann Oncol. 2025;36(7):775-785. doi:10.1016/j.annonc.2025.03.012
Kirshner G, Makai P, Brouns C, Timmers L, Kemp R. The impact of an 'evergreening' strategy nearing patent expiration on the uptake of biosimilars and public healthcare costs: a case study on the introduction of a second administration form of trastuzumab in The Netherlands. Eur J Health Econ. 2024;25(7):1147-1163. doi:10.1007/s10198-023-01648-w