Eleni Efstathiou, MD, Ph.D. of MD Anderson discusses an ASCO 2020 abstract entitled Neoadjuvant apalutamide (APA) plus leuprolide (LHRHa) with or without abiraterone (AA) in localized high-risk prostate cancer (LHRPC)
Context:
Novel androgen signaling inhibitors (ASIs) with medical castration could improve LHRPC outcomes. We have previously documented an association of relapse-free survival with pathologic tumor regression steps. However, a broad spectrum of recurrent cancers has been identified. A research investigating the APA effect in LHRPC was conducted to build on our findings and assess candidate outcome predictors.
Approaches:
This is a 6-month APA+LHRHa + /- AA (randomized 1:1) Phase II neoadjuvant analysis in LHRPC (cT2 + Gleason Score 8 or Gleason + PSA > 10 ng / mL) accompanied by radical prostatectomy (RP). The treatment effect was analyzed by pathology measurements [path. Step, volume of tumor (TV), percent of tumor cellularity (TC), volume of tumor epithelia (TEV: TC x TV)]. During the diagnostic biopsy IHC [AR signaling (AR-N, ARC19, ARV7, PSA), PTEN, glucocorticoid receptor (GR), Ki67, p53, RB] and DNA / RNA seq were assessed for tumor expression of candidate outcome markers. A predictive molecular signature (AR-N overexpression, nARV7 absence, no GR overexpression, Ki67 around 10 percent) previously described candidate was evaluated. The studies used were Univariate (Fisher ‘s exact, Wilcoxon) and Multivariate (logistic, linear models).
Reviews:
Sixty three had RP, out of the 65 pts enrolled. PS-ECOG 0, 65 (43-77) median age. Treatment with Grade 3 hypertension was well tolerated at 7 (2 APA + LHRHa). Presurgical PSA was approximately 0.1 in 62/63 (98%). In 13/32(41 percent) APA+LHRHa vs. 12/31 (39 percent) APA+A+LHRHa treated organ confined disease (uppercaseT2N0). Pathological full remission (APA+AA+LHRHa) was 2 (3%), minimal residual disease (5 on APA+LHRHa) was 6 (10%). Despite PSA response uniformity, we noted heterogeneity in tumor viability measurements: TV (0-11.5cc), TC (1-80 percent), TEV (0-6.1cc). ⇠ypT2N0 is correlated with prespecified molecular signature diagnostic biopsy positivity (p < 0.0001), PTEN expression (p: 0.004), absence of cribriform / intraductal distribution (p 0.002), but not with the Gleason Ranking. Only the prespecified biopsy signature associated with the result is used for multivariate analysis (p 0.003). Findings were repeated when TV, TC and TEV measurements were analyzed.
Findings:
In a subset of LHRPC patients, neoadjuvant Apalutamide + LHRHa is tolerable and results in tumor regression. Dual ASI care will not improve the results any more. Positive biopsy for a prespecified molecular signature associated with a response. The results of the study emphasize the need to take biological heterogeneity into account and to seek validation of response predictors in order to enhance therapeutic results in LHRPC. Details about clinical trials: NCT03279250.