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Updated: Jan 7, 2026
A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
Neoadjuvant pamiparib plus abiraterone and androgen deprivation therapy for high-risk/very high-risk localized
Tangtao Gong1,2, Shuo Liang1, Zhigang Wu1
1Department of Urology, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, China.
Background:
Androgen receptor signaling inhibition (ARPI) increases genomic instability of double-stranded DNA breaks, and co-inhibition of androgen receptor (AR) and poly(ADP-ribose) polymerase (PARP) induces synthetic lethality in multiple preclinical models. This phase II study evaluated the efficacy, safety, and quality-of-life (QoL) impact of neoadjuvant pamiparib plus abiraterone and androgen deprivation therapy (ADT) in patients with high-risk or very high-risk localized prostate cancer (HRPCa/VHRPCa).
Methods:
In this single-arm trial, patients with HRPCa/VHRPCa, defined as Gleason score ≥8, and/or cT3-4N0-1, and/or PSA ≥ 20 ng/mL, received pamiparib plus abiraterone and ADT for 4 months before radical prostatectomy (RP). The primary endpoint was pathological complete response (pCR; no residual tumor) or minimal residual disease (MRD; ≤5 mm residual tumor). Secondary endpoints included PSA response, surgical downstaging, 2-year biochemical progression-free survival (bPFS), QoL metrics, and safety.
Results:
Thirty patients were enrolled; 29 completed therapy and underwent RP. Median age was 65 years, and 9 patients had enlarged pelvic lymph nodes. Homologous recombination repair (HRR) mutations were detected in 7 patients. Overall, 8 patients (28%) achieved pCR or MRD (pCR in 3 [10%], MRD in 5 [17%]), and 18 patients (62%) had surgical downstaging, with no progression events. No significant difference in pCR or MRD rates was observed between patients with HRR mutations and those without HRR mutations. Two-year bPFS was 76%. FACT-P scores improved in 18 patients (62%) during therapy, with 9 of 22 (41%) maintaining improvement postoperatively. At 12 months, mean EPIC-26 urinary incontinence score was 83.2 ± 12.5. No grade 3-4 treatment-related adverse events occurred; common grade 1-2 events were anemia (45%), elevated AST/ALT (34%), and hypertriglyceridemia (45%).
Conclusions:
Neoadjuvant pamiparib plus abiraterone and ADT demonstrated efficacy, safety, and potential QoL benefits in HRPCa/VHRPCa.
Insights
Neoadjuvant pamiparib plus abiraterone and androgen deprivation therapy showed promising efficacy and safety in high-risk prostate cancer patients. This combination therapy improved outcomes and quality of life, warranting further investigation in localized prostate cancer.
Area of Science:
- Oncology
- Genitourinary Cancer
- Prostate Cancer Therapeutics
Background:
- Androgen receptor signaling inhibition (ARPI) enhances DNA damage, and combined AR and PARP inhibition shows synthetic lethality in preclinical prostate cancer models.
- High-risk localized prostate cancer (HRPCa/VHRPCa) requires novel neoadjuvant treatment strategies to improve outcomes.
- Evaluating pamiparib, abiraterone, and androgen deprivation therapy (ADT) offers a new therapeutic approach for HRPCa/VHRPCa.
Purpose of the Study:
- To assess the efficacy and safety of neoadjuvant pamiparib plus abiraterone and ADT in patients with HRPCa/VHRPCa.
- To evaluate the impact of this combination therapy on pathological complete response (pCR) or minimal residual disease (MRD).
- To determine the effects on quality of life (QoL), biochemical progression-free survival (bPFS), and surgical downstaging.
Main Methods:
- A single-arm, phase II clinical trial involving patients with HRPCa/VHRPCa.
- Patients received 4 months of neoadjuvant pamiparib, abiraterone, and ADT prior to radical prostatectomy (RP).
- Primary endpoint: pCR or MRD; Secondary endpoints: PSA response, surgical downstaging, 2-year bPFS, QoL, and safety.
Main Results:
- 28% of patients achieved pCR or MRD; 62% experienced surgical downstaging.
- Two-year bPFS was 76%, with improved QoL scores in 62% of patients during therapy.
- Common grade 1-2 adverse events included anemia (45%) and hypertriglyceridemia (45%); no grade 3-4 events occurred.
Conclusions:
- Neoadjuvant pamiparib plus abiraterone and ADT demonstrated significant efficacy and a favorable safety profile in HRPCa/VHRPCa.
- The combination therapy showed potential for improving pathological response and QoL.
- Further research is warranted to confirm these findings and explore the therapeutic potential in localized prostate cancer.
