Abstract P012: Genomic and clinical correlates of overall survival (OS) in men with newly diagnosed metastatic castration-sensitive prostate cancer (mCSPC) undergoing intensified androgen deprivation therapy (ADT)

Abstract

Abstract Background: Despite recent advancements in systemic therapy in men with mCSPC, disease remains fatal. Identification of novel genomic and clinical correlates of survival in this setting remain a significant unmet need. Methods: Newly diagnosed mCSPC undergoing intensified ADT i.e., ADT plus docetaxel or novel hormonal therapy and available tumor comprehensive genomic profiling (CGP) were included in the analysis. CGP was performed by a CLIA certified Next Generation Sequencing panel (Foundation Medicine) and involved the following genes: FAS, KDM6A, MYC1, PTEN, RB1, TMPRSS2, and TP53. All variants of unknown significance were removed, and mutated genes present in ≥5 % patients were included. Cox proportional hazards was used to assess relationships between OS and multiple variables (age at diagnosis, Gleason score, baseline PSA, de-novo disease, volume of disease, presence of visceral metastases and presence of genetic aberrations on CGP). Results: 127 patients were eligible and included. Higher baseline PSA (HR 1.45, 95% CI 1.09-1.9, P=0.0097), presence of visceral metastases (HR 4.41, 95% CI 1.26-15.39, P=0.0199) and genomic aberrations in MYC1 (HR 5.23, 95% CI 1.05-26.04, P=0.0433) and RB1 (HR 32.72, 95% CI 5.35-200.2, P=0.0002) were significantly associated with inferior OS. High volume disease trended to associate with poor OS, but was not statistically significant (HR 1.63, 95% CI 0.56-4.71, P=0.367). PTEN loss and other genomic aberrations were not associated with OS. See Table. Conclusions: In this real-world patient population of men with mCSPC undergoing intensified ADT we identify clinical and genomic markers associated with poor OS. This study has limitations as expected in a retrospective analysis. These data, upon external validation, may aid with development of a risk stratification model, counseling of patients, treatment decision making in the clinic, as well as further drug development. Citation Format: Nicolas Sayegh, Bennet Peterson, Roberto Nussenzveig, Adam Kessel, Taylor Ryan McFarland, Andrew Warren Hahn, Deepika Sirohi, Manish Kohli, Benjamin Louis Maughan, Umang Swami, Mark Yandell, Neeraj Agarwal. Genomic and clinical correlates of overall survival (OS) in men with newly diagnosed metastatic castration-sensitive prostate cancer (mCSPC) undergoing intensified androgen deprivation therapy (ADT) [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2021 Oct 7-10. Philadelphia (PA): AACR; Mol Cancer Ther 2021;20(12 Suppl):Abstract nr P012.