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

Area of Science:

• Oncology
• Immunotherapy
• Renal Cell Carcinoma Research

Background:

• Immune checkpoint inhibitors (ICI) have FDA approval for metastatic renal cell carcinoma (mRCC) in second-line (2015) and first-line (1L) settings (2018).
• Limited data exists on 1L ICI utilization in mRCC during off-label and post-FDA approval periods.

Purpose of the Study:

• To analyze the utilization of 1L ICI in mRCC patients in both off-label and post-FDA approval phases.
• To identify demographic and clinical factors associated with 1L ICI receipt before and after FDA approval.

Main Methods:

• Retrospective analysis of Medicare beneficiaries (≥66 years) diagnosed with mRCC (2015-2019).
• Definition of off-label vs. post-approval 1L ICI use based on the FDA approval date of ipilimumab/nivolumab (April 16, 2018).
• Multivariable logistic regression to examine associations between patient characteristics and 1L ICI receipt.

Main Results:

• 23,469 mRCC patients were identified; 2.4% received off-label 1L ICI, and 21% received post-approval 1L ICI.
• Off-label 1L ICI use was higher in patients with comorbidities (3+ conditions: OR=2.00).
• Post-approval, older (81+ vs. 66-70: OR=0.60) and frail patients were less likely to receive 1L ICI. No significant race/ethnicity differences were observed.

Conclusions:

• Initial off-label 1L ICI use in mRCC favored patients with comorbidities, but this trend shifted post-approval.
• After 1L ipilimumab/nivolumab approval, younger, healthier patients and those on dual-ICI regimens were more likely to receive 1L ICI.