MP-3 Molecular determinants associated with long-term response to apalutamide (APA) in nonmetastatic castration-resistant prostate cancer (nmCRPC)
Thursday June 27, 2019 from 21:45 to 22:15
Award Winner
Fred Saad, Canada has been granted the

Fred Saad, Canada

Professor and Chief of Urology


University of Montreal Health Centre (CHUM)


Molecular determinants associated with long-term response to apalutamide (APA) in nonmetastatic castration-resistant prostate cancer (nmCRPC)

Fred Saad1, Felix Y Feng2, Clemente Aguilar-Bonavides3, Justin Lucas4, Shibu Thomas3, Michael Gormley3, Sharon A McCarthy5, Sabine D Brookman-May6,7, Spyros Triantos3, Suneel Mundle5, Matthew R Smith8, Eric J Small2.

1Centre Hospitalier de l’Université de Montréal, University of Montreal, Montreal, QC, Canada; 2Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, United States; 3Janssen Research & Development, Spring House, PA, United States; 4Janssen Research & Development, Bridgewater, NJ, United States; 5Janssen Research & Development, Raritan, NJ, United States; 6Janssen Research & Development, Los Angeles, CA, United States; 7Ludwig Maximilians University, Munich, Germany; 8Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, United States

Introduction: SPARTAN, a phase 3 placebo (PBO)-controlled study in patients (pts) with nmCRPC, showed that APA plus androgen deprivation therapy (ADT) significantly improves metastasis-free survival compared with PBO + ADT. This exploratory analysis investigated potential biological signatures of pts with long-term responses to APA and PBO.

Methods: The biomarker cohort of SPARTAN was characterized as long-term responders (LTR) or early progressors (EP) based on time to metastasis, and separated into quartiles for APA and PBO groups. Pts progressing in the first quartile (APA, 21; PBO, 17), with shortest time to metastatic event, were classified as EP, those progressing in the last quartile (APA, 39; PBO, 20) as LTR. Gene expression profiles were generated from 233 archival primary prostate tumors. Predefined gene signatures indicative of cancer biology were compared between LTR and EP groups within the APA and PBO arms using 2 sample t tests. Signatures associated with LTR and EP were identified using p values of less than 0.05.

Results: Median time to metastatic progression was 40.5 months in APA pts and 22 months in PBO pts in the LTR group and 7.3 and 3.6 months in APA and PBO pts, respectively, in the EP group. Signatures were categorized into 3 general mechanistic classes, i.e., immune regulation, tumor vascularization, and hormone dependence. LTR on APA was associated with increased T cell activity reflected by T cell activation, stimulation, and antigen presentation, low proliferative capacity (p = 0.0435), and increased hormonal dependence (p = 0.0485). High proliferative, hormone nonresponsive tumors were associated with early progression on treatment with PBO.

Conclusions: Although this data requires confirmation in larger studies, the molecular determinants associated with LTR may have utility in selecting pts with nmCRPC who may derive the most benefit from APA and other androgen signaling inhibitors.

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