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Background <p>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).</p> Methods <p>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.</p> Results <p>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%).</p> Conclusions <p>Neoadjuvant pamiparib plus abiraterone and ADT demonstrated efficacy, safety, and potential QoL benefits in HRPCa/VHRPCa.</p>

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Neoadjuvant pamiparib plus abiraterone and androgen deprivation therapy for high-risk/very high-risk localized prostate cancer: an open-label, single-arm, phase 2 study

  • 期刊论文

  • 发表日期：

    2025年12月26日

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  • Tangtao Gong,
  • Shuo Liang,
  • Zhigang Wu,
  • Xuefeng Qiu,
  • Linfeng Xu,
  • Shan Peng,
  • Hongqian Guo,
  • Shun Zhang,
  • Junlong Zhuang

摘要

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.