Off-Label Use of First-Line Immunotherapy for Metastatic Renal Cell Carcinoma

Immune checkpoint inhibitors (ICI) were approved by the Food and Drug Administration (FDA) for patients with metastatic renal cell carcinoma (mRCC) in the second- line setting in 2015 and the first-line (1L) in 2018. Little is known about 1 L ICI use in the off-label (before FDA indication-specific approval) and postapproval settings.

We retrospectively analyzed off-label and post-FDA-approval 1 L ICI receipt in a cohort of Medicare beneficiaries ≥66 years old diagnosed with mRCC from 2015 to 2019. Off-label and postapproval 1 L ICI were defined as before or on/after 4/16/2018 (1L ipilimumab/nivolumab approval). Associations between demographic characteristics and 1 L ICI receipt in the off-label and postapproval periods were examined using multivariable logistic regression.

We identified 23,469 patients, of which 368 (2.4%) off-label and 1,663 (21%) postapproval received 1 L ICI. In the off-label period, patients with co-morbid conditions were more likely to receive 1 L ICI compared to patients with no co-morbidities (3+ conditions, OR = 2.00; 95% CL, 1.31-3.05). In the postapproval period, older patients were less likely to receive 1 L ICI (81+ vs. 66-70, OR = 0.60; 95% CL, 0.52-0.69), and patients who were frail were less likely to receive 1 L ICI (OR = 0.77; 95% CL, 0.69-0.87). There were not significant differences in 1 L ICI receipt based on race/ethnicity.

Older patients and patients with more comorbidities were more likely to receive 1 L ICI off-label, but these differences did not persist after FDA approval. After 1 L ipilimumab/nivolumab approval, patients receiving 1 L ICI were more likely younger, healthy, and receiving dual-ICI regimens.