Deciphering radiological stable disease to immune checkpoint inhibitors

Area of Science:

• Oncology
• Immunotherapy
• Clinical Trial Analysis

Background:

• Stable disease (SD) is a frequent but poorly understood outcome in patients receiving immune checkpoint inhibitors (ICIs).
• Characterizing SD is crucial for advancing drug development and correlative research in ICI therapy.

Purpose of the Study:

• To define and characterize stable disease (SD) in patients undergoing immune checkpoint inhibitor (ICI) treatment.
• To identify a subset of patients with SD who demonstrate meaningful clinical benefit from ICIs.
• To propose a refined definition of SD that improves the precision of clinical and translational research.

Main Methods:

• Conducted a systematic review of ICI trials to analyze SD.
• Compared SD and objective response with proliferation index using The Cancer Genome Atlas gene expression data.
• Defined a subgroup of SD patients with outcomes similar to responders in non-small-cell lung cancer (NSCLC) discovery and validation cohorts, using progression-free survival (PFS) and tumor growth criteria.

Main Results:

• SD occurred in 16-42% of patients across various tumor types in ICI trials and correlated with tumor proliferation index, not ICI response.
• In NSCLC patients with SD, progression-free survival (PFS) varied widely (0.2-49 months).
• A subset of SD patients with PFS >6 months and no tumor growth showed survival mirroring partial response and was proposed as 'SD responders', validated in external cohorts.

Conclusions:

• RECIST-defined SD in immunotherapy is heterogeneous, often reflecting tumor growth rate rather than ICI efficacy.
• Patients with NSCLC experiencing SD with PFS >6 months and no tumor growth may be classified as 'SD responders'.
• This refined definition of SD responders can enhance the efficiency and insights gained from clinical and translational research in immunotherapy.