The authors performed a retrospective analysis of 309 consecutive patients with CRPC treated with first-line abiraterone or enzalutamide. Of these, 116 men (38%) had available tumor tissue for analysis, and formed the basis of this study. Deleterious TP53 missense mutations and PTEN deletions were interrogated using genetically validated immunohistochemical assays for p53 protein nuclear accumulation and PTEN protein loss. Overall survival (OS) and progression-free survival (PFS) were compared between patients with and without p53 and/or PTEN alterations.
46% of evaluable cases had PTEN loss and 27% had p53 nuclear accumulation. 45% (53/118) of cases underwent targeted next generation sequencing and p53 nuclear accumulation was 91% sensitive and 90% specific for underlying TP53 missense mutation. OS and PFS did not differ significantly according to PTEN status but were associated with p53 status. Median OS was 15.8 months (95% CI, 15.8–23.9) and 28.7 months (95% CI, 28.7–42.7) for men with and without p53 nuclear accumulation, respectively (HR 1.98; P = 0.007). Median PFS was 5.5 months (95% CI, 3.53–10.5 months) and 10.2 months (95% CI, 7.37–13.3 months) in men with and without p53 nuclear accumulation, respectively (HR 1.73; P = 0.013). In multivariable analyses, p53 status was independently associated with both OS (HR 2.13; P = 0.016) and PFS (HR 1.83; P = 0.034). This effect was also seen in the subset of patients with prostatectomy tissue only. In patients with p53 nuclear accumulation median PFS (p < 0.001) and median OS (p < 0.001) were decreased compared to wild-type patients. No effect was seen with PTEN loss in either PFS (p = 0.12) or OS (p = 0.50).
In summary, p53 status may be a biomarker of sensitivity to novel hormonal therapies in CRPC. PTEN was not a biomarker of sensitivity in this study. These results require prospective validation.
Presented By: Benjamin Louis Maughan, MD, PharmD, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT
Written By: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre, Toronto, Ontario, Canada
at the 2017 ASCO Annual Meeting - June 2 - 6, 2017 - Chicago, Illinois, USA