Experience With Subcutaneous PD-L1 Inhibitor
Panelists discuss how the IMscin001 trial findings established subcutaneous atezolizumab noninferiority with comparable efficacy and safety to intravenous (IV) formulation while highlighting operational challenges, including creating multiple electronic medical record (EMR) order sets, standardizing injection times and volumes across products, and addressing nursing workflow considerations during the 2- to 10-minute injection periods.
Atezolizumab Subcutaneous Data and Implementation Considerations
The subcutaneous formulation of atezolizumab (PD-L1 inhibitor) received approval approximately 1 year ago based on the IMscin001 phase 3 open-label study findings. This trial enrolled patients with locally advanced or metastatic non–small cell lung cancer who had progression on first-line platinum therapy, randomly assigning them 2:1 to receive subcutaneous atezolizumab every 3 weeks (administered over less than 10 minutes into anterior thigh subcutaneous tissue, 15-mL injection volume) vs IV formulation. Coprimary pharmacokinetic end points assessed cycle 1 trough concentration and model-predicted area under the curve (AUC) from days 0 to 21. Secondary end points evaluated steady-state exposure, efficacy (objective response rate, progression-free survival, overall survival), safety, and immunogenicity.
The trial met both coprimary end points, with geometric mean ratios (GMRs) demonstrating noninferiority. The GMR for cycle 1 trough was 1.05 (range, 0.881-1.24), and AUC from 0 to 21 days was 0.87, exceeding the prespecified lower threshold of 0.8. Efficacy outcomes showed comparable objective response rates (9% subcutaneous vs 8% IV) with no meaningful differences in progression-free survival or overall survival between arms. Serious adverse events were comparable between formulations. Injection site reactions occurred in 4.5% of patients receiving subcutaneous administration, predominantly mild and transient, consistent with the nivolumab experience. The data statistically support equivalency while offering operational benefits for appropriate patient populations, particularly those on maintenance monotherapy or adjuvant treatment without combination chemotherapy.
Implementation challenges emerge around standardization of administration protocols and EMR infrastructure. Building multiple subcutaneous injection order sets requires careful attention to dose-specific details, FDA approval indications, and precise International Classification of Diseases,
Tenth Revision coding for each formulation. Significant variability exists across products in administration time (2-10 minutes), injection volumes, and specific procedural requirements based on how each product was studied in clinical trials. This creates complexity for nursing staff, who must remember product-specific protocols. Opportunity exists for establishing standardized subcutaneous administration rates based on injection volume categories (eg, < 5 mL over 1 minute, 5.1-10 mL over 2-3 minutes) to enhance staff experience and workflow consistency. An additional consideration involves nursing time allocation: Subcutaneous injections require nurses to remain with patients throughout the 2- to 10-minute administration period, whereas IV infusions allow nurses to initiate therapy and attend to other tasks during the 30-minute infusion. Solutions may include specialized injection devices (similar to those being developed for CD38-targeted therapies such as daratumumab) that can deliver subcutaneous products without requiring continuous nursing presence, potentially applicable across various volumes and products to standardize administration further.
