Abstract
e17594 Background: mPC is a dynamic disease that confers a poor prognosis- particularly in the metastatic castration-resistant prostate cancer (mCRPC) setting. Analysis of ctDNA provides an opportunity to identify and monitor somatic alterations (SAs) in a patient’s treatment course. However, how certain SAs can inform disease management is not fully characterized. We evaluated whether the presence of specific gene amplifications (GAs) and changes in plasma copy number (PCN) are associated with disease features and prognosis. Methods: This is a retrospective study of mPC patients seen at the Hollings Cancer Center between 2015-2019 who underwent ctDNA profiling using Guardant360 (Guardant Health Inc). Guardant360 identifies SAs and GAs of select genes by NGS. Descriptive statistics were used to summarize baseline patient characteristics. The chi-square test and odds ratio (OR) were used to evaluate associations between clinical factors and GAs. The Kaplan-Meier method was used to estimate OS from either the date of GA detection or the initiation of systemic therapy. Results: 130 men with mPC were identified as having ≥1 GA. The presence of liver and/or lung metastases were associated with GAs of BRAF (OR 2.5; 95%CI 1.1-5.8, p < 0.05) , CDK6 (OR 2.3; 95%CI 1.4-8.0, p < 0.01) , PI3KCA (OR 4.4; 95%CI 1.8-10.7, p < 0.01) , and FGFR1 (OR 3.1; 95%CI 1.1-9.0, p = 0.038). These GAs were also associated with having ≥2 concurrent GAs (p < 0.01 for each gene). From this cohort, survival analyses were completed on 59 patients with mCRPC. Men with only 1 GA, compared to men with ≥2 GAs, had improved median survival (mo.) from date of initial GA(s) detection (16.5 vs 9.4, p < 0.01) or therapy initiation (16.0 vs 9.0, p < 0.01). Among men with mCRPC, AR and/or MYC GA, median survival improved in men who had reduction in AR or MYC PCN during therapy compared to men without a PCN decrease (25.1 vs 15.9 p < 0.01). Conclusions: Patients with mPC who had liver and/or lung metastases were associated with having specific GAs in BRAF, CDK6, PI3KCA, and FGFR1. Notably, the presence of liver or lung metastases was not associated with AR GA. In mCRPC, patients with ≥2 GAs had decreased OS compared to men with one GA. Having an increased number of GAs is likely reflective of greater chromosomal instability and be associated with more aggressive disease. Our study reveals serial monitoring of AR and MYC PCN during therapy demonstrated reduced OS in patients without PCN reduction. This supports the use of serial ctDNA monitoring of PCN to inform therapeutic response and prognosis.
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call