Assessing the Increased Variability in Individual Lesion Kinetics During Immunotherapy: Does It Exist, and Does It...

Area of Science:

• Oncology
• Clinical Pharmacology
• Biostatistics

Background:

• Immunotherapy's impact on individual lesion kinetics remains unclear.
• The sum of the longest diameter may not accurately reflect treatment response due to lesion variability.
• Understanding within-patient variability is crucial for accurate assessment of treatment efficacy.

Purpose of the Study:

• To investigate if immunotherapy exacerbates lesion kinetic variability.
• To develop a model for estimating sources of variability in lesion kinetics.
• To evaluate the impact of lesion variability on patient survival.

Main Methods:

• A semimechanistic model was used to analyze nonlinear lesion kinetics and survival risk.
• The model incorporated between- and within-patient variability using random effects.
• Data from 900 patients in the IMvigor211 trial (atezolizumab vs. chemotherapy) were analyzed.

Main Results:

• Within-patient variability accounted for 12%-78% of total variability in lesion kinetics.
• Within-patient variability in treatment durability was higher with atezolizumab (40%) than chemotherapy (12%).
• Divergent lesion profiles increased over time with atezolizumab, reaching ~20% after 1 year.
• Accounting for within-patient variability improved prediction of at-risk patients compared to sum of longest diameter.

Conclusions:

• Within-patient variability in lesion kinetics is significant in metastatic urothelial carcinoma.
• This variability is particularly pronounced with programmed death-ligand 1 (PD-L1) checkpoint inhibitor immunotherapy.
• Within-patient variability offers valuable insights for assessing treatment efficacy and identifying at-risk patients.