A molecular signature has been identified that may identify long-term respondents from treatment with apalutamide (Erleada) and androgen deficiency androgen (ADT) in patients with prostate cancer versus non-astrostatic castration (ADH). nmCRPC), according to conclusions, presented at Genitourinary Cancer 2021 Symposium.1
Data were taken from a randomized controlled trial of placebo, placebo-controlled SPARTAN test (NCT01946204). At the last analysis of SPARTAN, treatment with apalutamide plus ADT increased overall median survival by 14 months versus placebo plus ADT in patients with nmCRPC.2 Based on initial data from the SPARTAN trial, the FDA approved apalutamide in 2018 for used in this situation.
For the current study, researchers identified patients in the SPARTAN biomarker population as long-term responders (LTRs) or early promoters (EPs). Patients from the apalutamide plus ADT and placebo plus ADT groups were placed in quartiles based on number and time of metastatic events. Patients who did not progress or reached a metastatic event after the third quarter were considered LTRs, whereas patients who had a metastatic event in the first quarter were considered as EPs.
“Because patients in the placebo group had previously undergone androgen-only poverty treatment, our analysis focused only on the long-term response population treated with apalutamide. in addition to androgen-poverty, ”said study researcher Felix Y. Feng, MD, professor of radiation oncology, urology, and medicine at the University of California, San Francisco and director of the Benioff Initiative for Prostate Cancer Research at Helen Family Comprehensive Cancer Center Diller.
The SPARTAN biomarker population included 233 tumors collected at radical prostatectomy or during diagnostic biopsies. “A gene expression profile was used to identify molecular subtypes in the group, based on a selected number of predefined signatures representing specific biological pathways or processes relevant to prostate cancer,” Feng said.
A. t a test method was used to study different expressions in the LTR and EP groups. Names indicating stated statistical significance were identified. In parallel, a Cox proportional risk model was applied to the entire biomarker population to determine whether these signatures were associated with survival without metastasis (MFS). The reviewers then looked at signatures associated with a response to treatment by both analyzes. Names that were both differentially expressed in LTRs versus EPs and had a specific effect on treatment on clinical outcome were identified as predictive biomarkers in response to treatment, Feng said.
“Among patients treated with apalutamide, independent names were associated with a long-term response with molecular names that showed increased immune activity, reduced vascularization, or decreased proliferative capacity at baseline. None of these names were associated with a long-term placebo response, ”said Feng.
In the placebo group, increased hormonal independence and metastatic potential at baseline were associated with early progression.
Feng reported that signatures associated with a long-term response to apalutamide plus ADT were also associated with increased MFS with Cox withdrawal.
“In particular, signatures of baseline T cell proliferation and T cell stimulation were increased in patients with a long-term response,” Feng said.
The researchers also found that patients with basal tumors with higher levels of T cell proliferation appeared to have a similar benefit to apalutamide plus ADT compared to patients with luminal tumors.
References
1. Feng FY, Aguilar-Bonavides C, Lucas J, et al. Molecular determinants associated with long-term response to apalutamide (APA) in anti-spasm-resistant prostate cancer (nmCRPC). J Clin Oncol. 2021; 39 (solair 6): 8. doi: 10.1200 / JCO.2021.39.6_suppl.8
2. Smith MR, Saad F, Chowdhury S, et al. Apalutamide and overall survival in prostate cancer. Eur Urol. 2021; 79 (1): 150-158. doi: 10.1016 / j.eururo.2020.08.011