FDA不批准他拉唑帕利加恩杂鲁胺治疗非HRR基因突变的mCRPC

近年来，前列腺癌的精准治疗取得了显著进展，尤其是针对HRR基因突变患者的靶向治疗策略。然而，对于非HRR基因突变患者，仍存在较大的治疗空白。他拉唑帕利（Talazoparib）与恩杂鲁胺（Enzalutamide）的联合疗法在2023年获得FDA批准用于HRR基因突变的转移性去势抵抗性前列腺癌（mCRPC）患者，但其在非HRR突变患者中的疗效尚未得到充分验证。

根据TALAPRO-2试验的数据，尽管该组合在HRR突变患者中表现出显著的生存获益，但在非HRR突变患者中未达到统计学意义的改善。FDA的Oncologic Drugs Advisory Committee（ODAC）在2025年的会议上一致认为该组合在非HRR突变患者中的风险-获益比不具优势。此外，虽然TALAPRO-2试验的更新数据表明，在非HRR突变患者中，联合治疗组的中位总生存期（OS）为45.8个月，对照组为37个月（HR=0.80），但仍不足以支持扩大适应症。因此，Pfizer决定不再在美国申请该组合在非HRR突变患者中的适应症。

此次FDA的决策强调了精准医疗在肿瘤治疗中的重要性，同时也凸显了在非特定分子亚型患者中开展临床试验的挑战。尽管如此，TALAPRO-2试验的长期随访数据仍为HRR突变患者提供了有力的证据支持。未来研究可能需要探索更多生物标志物或联合其他靶向药物以提高非HRR突变患者的治疗效果。

来源: urologytimes

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