Leuprolide Plus Apalutamide as Neoadjuvant Therapy for Prostate Cancer
Posted: Tuesday, July 28, 2020
Combining leuprolide with apalutamide in the neoadjuvant setting resulted in tumor regression in a subset of patients with localized high-risk prostate cancer, in a phase II trial; however, dual androgen signaling inhibition with abiraterone did not improve outcomes. Eleni Efstathiou, MD, PhD, of the MD Anderson Cancer Center, Houston, and colleagues presented these results during the ASCO20 Virtual Science Program (Abstract 5504).
“Study results emphasize the need to consider biologic heterogeneity and pursue validation of predictors of response to improve therapeutic outcomes in localized high-risk prostate cancer,” concluded the authors.
This trial recruited 65 patients with locally advanced prostate cancer who were randomly assigned 1:1 to receive apalutamide and leuprolide with or without abiraterone. After treatment, 63 of the 65 patients underwent radical prostatectomy. Tumor markers were measured using DNA/RNA sequencing as well as immunohistochemistry.
The PSA level was less than 0.1 ng/mL in 98% of patients, whereas organ-confined disease was seen in 41% of patients receiving leuprolide plus apalutamide and 39% of patients receiving concurrent abiraterone. There were two patients in the triplet-therapy arm who achieved pathologic complete remission, and five patients in the dual-therapy group had minimal residual disease.
In addition, heterogeneity was noted in measures of tumor viability, such as tumor volume, tumor cellularity, and tumor epithelial volume. An association was found between patients with a tumor stage less than or equal to T2N0 and a biopsy positive for the expression of androgen receptor signaling, PTEN expression, glucocorticoid receptors, p53, RB, and the absence of intraductal disease spread. This biopsy signature was associated with outcome.
Overall, the treatment was well tolerated. The sole reported adverse event was grade 3 hypertension in seven patients (two in the apalutamide-and-leuprolide group, and six in the abiraterone group).
Disclosure: For full authors’ disclosures, visit coi.asco.org.