LBA02-11 MASITINIB PLUS DOCETAXEL AS FIRST-LINE TREATMENT OF METASTATIC CASTRATE REFRACTORY PROSTATE CANCER: RESULTS FROM STUDY AB12003

Abstract

You have accessJournal of UrologyLate-breaking Abstract II - Malignant1 Sep 2021LBA02-11 MASITINIB PLUS DOCETAXEL AS FIRST-LINE TREATMENT OF METASTATIC CASTRATE REFRACTORY PROSTATE CANCER: RESULTS FROM STUDY AB12003 Michel Pavic, Olivier Hermine, and Dominique Spaeth Michel PavicMichel Pavic More articles by this author , Olivier HermineOlivier Hermine More articles by this author , and Dominique SpaethDominique Spaeth More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002149.11AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Masitinib (MAS) is an oral, small molecule drug that targets mast cell and macrophage activity. These innate immune cells are critical components of the tumor microenvironment and are associated with prostate cancer progression. METHODS: AB12003 was a prospective, placebo (PBO) controlled, double blind, randomized, phase 3 trial, evaluating MAS (6.0 mg/kg/d) in combination with docetaxel (DTX) (IV 75 mg/m2 plus prednisone for up to 10 cycles) as a first-line treatment of metastatic castrate resistant prostate cancer (mCRPC). Eligible patients (pts) were chemo-naïve with confirmed mCRPC, who had progressed on previous abiraterone treatment or were indicated for DTX treatment, and had a ECOG ≤1. Primary analysis was performed on a pre-specified targeted subgroup, defined as pts with baseline alkaline phosphatase levels (ALP) ≤250 IU/ml, and on the overall population. Primary endpoint was progression free survival (PFS) (PCWG2 definition). The study was successful if improvement in median PFS relative to control reached a 3.9% level of significance for the target subgroup (alpha split with fallback procedure to conserve overall type-I error at 5% for the overall study cohort). RESULTS: A total of 714 pts were enrolled (safety population n=712). In the targeted (ALP ≤250) subgroup, MAS-DTX (n=225) showed significant benefit over PBO-DTX (n=225) with median PFS of 6.3 months (96.1% CI [5.6;7.6]) vs 5.4[4.6;6.0] months; p=0.0272. The hazard ratio (HR) was 0.79 [0.64;0.97], p=0.0087), a significant 21% reduction in risk of progression for MAS-DTX pts relative to control. Assessment of PFS rates was convergent with this primary outcome; 12, 18, and 24-month PFS rates showed significant 1.6-fold (p=0.0035), 1.9-fold (p=0.0001) and 1.9-fold (p=0.0028) improvement, respectively, in favor of MAS-DTX (ie, 32.0%, 27.6% and 23.1% for MAS-DTX vs 19.6%, 14.6% and 12.0% for PBO-DTX). There was no benefit on overall survival (OS) in the targeted subgroup. Regarding the overall population (ie, irrespective of ALP), no PFS or OS benefit was observed; median PFS for MAS-DTX (n=355) was 5.7 months (95% CI [4.9;6.3]) vs 5.4[4.6;5.9] months for PBO-DTX (n=357), p=0.2977. The proportion of pts presenting at least one adverse event (AE), severe AE or serious AE was respectively, 96.6%, 79.2% and 27.6% for MAS-DTX (n=355) vs 96.4%, 73.1% and 18.8% for PBO-DTX (n=357). CONCLUSIONS: The combination MAS (6.0 mg/kg/d) plus DTX may provide a new first-line treatment option for mCRPC pts with ALP ≤250 IU/ml. Source of Funding: AB Science, France © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e1179-e1179 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Michel Pavic More articles by this author Olivier Hermine More articles by this author Dominique Spaeth More articles by this author Expand All Advertisement Loading ...