Slootbeek Peter H J, Kloots Iris S H, van Oort Inge M, Kroeze Leonie I, Schalken Jack A, Bloemendal Haiko J, Mehra Niven
Department of Medical Oncology, Radboud University Medical Center, Geert Grooteplein-Zuid 10, 6525 GA Nijmegen, The Netherlands.
Department of Urology, Radboud University Medical Center, Geert Grooteplein-Zuid 10, 6525 GA Nijmegen, The Netherlands.
Cancers (Basel). 2023 May 18;15(10):2814. doi: 10.3390/cancers15102814.
Patients with metastatic castration-resistant prostate cancer (mCRPC) harbouring homologous recombination repair-related gene aberrations (HRRm) can derive meaningful benefits from both platinum-based chemotherapy (PlCh) and PARP inhibitors (PARPi). Cross-resistance between these agents is well-recognised in other tumour types but data on prostate cancer is lacking. In this retrospective pre-planned study, we assessed 28 HRRm mCRPC patients who received PlCh and PARPi. Progression-free survival (PFS) on initial therapy was longer than on subsequent therapy (median 5.3 vs. 3.4 months, = 0.016). The median PFS of PlCh was influenced by the order of agents, with 3.6 months shorter PFS after PARPi than when administered first. The median PFS of PARPi was less influenced, with 0.9 months shorter PFS after PlCh than before. In the PARPi-first subgroup, six out of 16 evaluable patients (37.5%) had a >50% PSA decline to PlCh, and two of eight (25.0%) had a radiographic response to PlCh. In the PlCh-first subgroup, 6/10 (60.0%) had a >50% PSA decline, and 5/9 (55.6%) had a radiographic response to PARPi. These data show >40% of the cohort is sensitive to a subsequent HRR-targeting agent. PlCh appears to induce less cross-resistance than PARPi. Additional data on resistance mechanisms will be crucial in defining an optimal treatment sequence in HRRm mCRPC patients.
携带同源重组修复相关基因畸变（HRRm）的转移性去势抵抗性前列腺癌（mCRPC）患者可从铂类化疗（PlCh）和PARP抑制剂（PARPi）中获得显著益处。这些药物之间的交叉耐药在其他肿瘤类型中已得到充分认识，但前列腺癌方面的数据尚缺乏。在这项回顾性预先计划的研究中，我们评估了28例接受PlCh和PARPi治疗的HRRm mCRPC患者。初始治疗的无进展生存期（PFS）长于后续治疗（中位值5.3个月对3.4个月， = 0.016）。PlCh的中位PFS受用药顺序影响，PARPi后使用时PFS比先使用时短3.6个月。PARPi的中位PFS受影响较小，PlCh后使用时PFS比之前短0.9个月。在PARPi优先治疗亚组中，16例可评估患者中有6例（37.5%）对PlCh的PSA下降>50%，8例中有2例（25.0%）对PlCh有影像学反应。在PlCh优先治疗亚组中，10例中有6例（60.0%）的PSA下降>50%，9例中有5例（55.6%）对PARPi有影像学反应。这些数据表明，超过40%的队列对后续的HRR靶向药物敏感。PlCh似乎比PARPi诱导的交叉耐药更少。关于耐药机制的更多数据对于确定HRRm mCRPC患者的最佳治疗顺序至关重要。
