Prostate Cancer Coverage from Every Angle

AACR 2021: Exploratory Analysis of Molecular Signatures From TITAN Trial in Prostate Cancer

By: Vanessa A. Carter, BS
Posted: Friday, April 30, 2021

During the virtual edition of the American Association for Cancer Research (AACR) Annual Meeting 2021, Neeraj Agarwal, MD, of Huntsman Cancer Institute, University of Utah, Salt Lake City, and colleagues presented their findings from an exploratory analysis of the molecular signatures of long-term responders to apalutamide from the TITAN trial—a phase III, placebo-controlled study in metastatic castration-sensitive prostate cancer (Abstract 359). When added to androgen-deprivation therapy (ADT), apalutamide demonstrated a consistent clinical benefit, suggesting that molecular signatures may be useful in identifying patients who would derive the most benefit.

“These results suggest that patients with metastatic castration-sensitive prostate cancer who have relatively lower levels of myeloid-derived suppressor cells in the tumor, indicative of a less immune-suppressed tumor microenvironment, may have long-term benefit from treatment with apalutamide,” concluded the researchers. However, they noted, larger studies are needed for confirm their findings.

This study analyzed primary prostate tumors from 222 patients with metastatic castration-sensitive prostate cancer who were on ADT; patients were administered either apalutamide or a placebo. Individuals were further characterized as either early progressors or long-term responders based on radiographic progression-free survival (shortest vs. longest).

The median follow-up was 22.7 months. The median radiographic progression-free survival was not met for long-term responders to apalutamide, but those given a placebo had a survival of 32.9 months. In the early-progressor group, patients given apalutamide and a placebo had progression-free survivals of 10.9 and 3.7 months, respectively.

In both cohorts, there seemed to be a higher level of expression of either the Decipher signature or polycomb repressive complex 2 activation for those in the early-progressor group. For long-term responders to apalutamide, lower expression of transcriptional signatures describing cell-cycle progression and myeloid-derived suppressor cells was observed.

Disclosure: For full disclosures of the study authors, visit

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