Potential insights from population kinetic assessment of progression-free survival curves. (September 2020)

• Record Type: Journal Article
• Authors: Stewart, David J.; Bosse, Dominick; Robinson, Andrew; Ong, Michael; Fung-Kee-Fung, Michael; Brule, Stephanie; Hilton, John F.; Ocana, Alberto
• Is Part Of: Critical reviews in oncology/hematology. Volume 153(2020)
• Publication Date: 2020-09
• Subjects: Population kinetics -- Progression-free survival curve shape; Oncology -- Periodicals; Hematology -- Periodicals; 616.994
• DOI: 10.1016/j.critrevonc.2020.103039
• Languages: English
• ISSNs: 1040-8428

Abstract

Graphical abstract: Highlights: Progression-free survival (PFS) curves can be fit by first order kinetics models. Shape of PFS curve log-linear plots differs significantly by therapy type. These PFS curve log-linear plot differences offer biological insights. A rightward deflection on a log-linear plot suggests 2 distinct subpopulations. A downward deflection reflects accelerated progression due to therapy interruption. Abstract: Progression-free survival (PFS) curves follow first order kinetics on exponential decay nonlinear regression analysis (EDNLRA). Some exhibit 1-phase-decay, some have 2-phase-decay, some are convex. We digitized, performed EDNLRA and generated log-linear plots for 887 published PFS curves for incurable solid tumors treated with various systemic therapies. Proportion of curves fitting 2-phase-decay varied by therapy (p < 0.0001). For 13 therapies, > 64 % of PFS curves had 2-phase-decay. This included epidermal growth factor receptor inhibitors in unselected lung cancer patients (some with, some without mutations), immune checkpoint inhibitors, interferon, breast cancer hormonal therapies, and selected others, suggesting 2 distinct, potentially identifiable subpopulations with differing progression rates. For 22 other therapies, < 25 % of PFS curves had 2-phase-decay. Only 1 therapy was in the mid-range. Small cell lung and colon carcinomas were particularly likely to yield highly convex curves (p < 0.006), probably from discontinuation of effective therapies. PFS curve shape may yield biological and clinical insights.