Tumor Response to Stroma-Modifying Therapy: Magnetic Resonance Imaging Findings in Early-Phase Clinical Trials of Pegvorhyaluronidase alpha (PEGPH20).

Autor: Arias-Lorza AM; Moffitt Cancer Center., Costello JR; Moffitt Cancer Center., Hingorani SR; University of Nebraska Medical Center., Von Hoff DD; Translational Genomics Research Institute (TGen)., Korn RL; Imaging Endpoints Core Lab., Raghunand N; Moffitt Cancer Center.
Jazyk: angličtina
Zdroj: Research square [Res Sq] 2023 Sep 05. Date of Electronic Publication: 2023 Sep 05.
DOI: 10.21203/rs.3.rs-3314770/v1
Abstrakt: Pre-clinical and clinical studies have shown that PEGPH20 depletes intratumoral hyaluronic acid (HA), which is linked to high interstitial fluid pressures and poor distribution of chemotherapies. 29 patients with metastatic advanced solid tumors received quantitative magnetic resonance imaging (qMRI) in 3 prospective clinical trials of PEGPH20, HALO-109-101 (NCT00834704), HALO-109-102 (NCT01170897), and HALO-109-201 (NCT01453153). Apparent Diffusion Coefficient of water (ADC), T1, k trans , v p , v e , and iAUC maps were computed from qMRI acquired at baseline and ≥ 1 time point post-PEGPH20. Tumor ADC and T1 decreased, while iAUC, k trans , v p , and v e increased, on day 1 post-PEGPH20 relative to baseline values. This is consistent with HA depletion leading to a decrease in tumor water content and an increase in perfusion, permeability, extracellular matrix space, and vascularity. Baseline parameter values that were predictive of pharmacodynamic responses were: ADC > 1.46×10 -3 mm 2 /s (Balanced Accuracy (BA) = 72%, p < 0.01), T1 > 0.54s (BA = 82%, p < 0.01), iAUC < 9.2 mM-s (BA = 76%, p < 0.05), k trans <0.07min -1 (BA = 72%, p = 0.2), v e <0.17 (BA = 68%, p < 0.01), and v p <0.02 (BA = 60%, p < 0.01). Further, v e <0.39 at baseline was moderately predictive of response in any parameter (BA = 65.6%, p < 0.01 averaged across patients). These qMRI biomarkers are potentially useful for guiding patient pre-selection and post-treatment follow-up in future clinical studies of PEGPH20 and other tumor stroma-modifying anti-cancer therapies.
Competing Interests: Competing Interests Statement NR received a research grant from Halozyme Therapeutics for the work reported here. SRH and DDVH received funding to their institutions from Halozyme to defray study-related costs. RLK is Founder and CEO of Imaging Endpoints, LLC. No potential conflicts of interest were disclosed by the other authors. The data analyses reported here remained under the full control of the authors.
Databáze: MEDLINE
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