Experience With Subcutaneous PD-L1 Inhibitor

Subcutaneous atezolizumab, approved approximately 1 year prior based on the IMscin001 phase 3 study, extends subcutaneous immune checkpoint inhibitor options to PD-L1 inhibition in patients with locally advanced or metastatic non–small cell lung cancer following platinum therapy progression. The trial randomly assigned patients 2:1 to receive subcutaneous atezolizumab administered over less than 10 minutes via 15-mL anterior thigh injection vs standard intravenous (IV) formulation every 3 weeks. Coprimary pharmacokinetic end points included cycle 1 trough concentration and model-predicted area under curve (AUC) from day 0 to 21, with secondary end points evaluating steady-state exposure, efficacy, safety, and immunogenicity.

The IMscin001 trial successfully met both coprimary pharmacokinetic end points, with geometric mean ratios demonstrating equivalency above the prespecified 0.8 threshold: 1.05 for cycle 1 trough concentration and 0.87 for AUC. Efficacy outcomes showed comparable results between formulations, with objective response rates of 9% for subcutaneous vs 8% for IV administration, and no meaningful differences in progression-free survival or overall survival. These findings mirror the pattern established with subcutaneous nivolumab, providing additional evidence that subcutaneous delivery maintains therapeutic efficacy across different immune checkpoint inhibitor mechanisms.

Safety evaluation revealed comparable serious adverse events between subcutaneous and IV atezolizumab, with injection site reactions reported in 4.5% of patients receiving subcutaneous administration—slightly lower than the 8% observed with subcutaneous nivolumab. These reactions remained predominantly mild and transient, consistent with the safety profile established across subcutaneous immune checkpoint inhibitor trials. Health care providers note that operational benefits, quality of life improvements, and efficacy remain consistent across subcutaneous formulations, though implementation challenges include building multiple indication-specific order sets with precise dosing, FDA approval specifications, and International Classification of Diseases, Tenth Revision, coding requirements within electronic medical record systems—work that requires substantial pharmacy and information technology coordination.