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佩米替尼 - 版本历史
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2026-01-09T04:39:04Z
<p>建立内容为“<div style="padding: 0 4%; line-height: 1.8; color: #1e293b; font-family: 'Helvetica Neue', Helvetica, 'PingFang SC', Arial, sans-serif; background-color: #ffffff…”的新页面</p>
<p><b>新页面</b></p><div><div style="padding: 0 4%; line-height: 1.8; color: #1e293b; font-family: 'Helvetica Neue', Helvetica, 'PingFang SC', Arial, sans-serif; background-color: #ffffff; max-width: 1200px; margin: auto;"><br />
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<strong>[[佩米替尼]]([[Pemigatinib]])</strong>，商品名为<strong>[[达伯坦]]([[Pemazyre]])**，研发代码为**[[INCB054828]]</strong>，是由[[Incyte]]公司研发（中国区由[[信达生物]]协作）的一种强效、口服、选择性<strong>[[FGFR1/2/3抑制剂]]</strong>。作为全球首个获批用于治疗携带<strong>[[FGFR2基因融合]]</strong>或重排的晚期<strong>[[肝内胆管癌]]</strong>（[[iCCA]]）的靶向药物，[[佩米替尼]]通过ATP竞争性抑制机制阻断激酶自磷酸化。临床研究<strong>[[FIGHT-202]]</strong>证实了其在化疗进展后的显著疗效。该药物的应用确立了胆道系统肿瘤“**[[分子分型引领]]**”的诊疗范式，并在<strong>[[高磷血症]]</strong>管理及眼科安全性监测方面建立了成熟的临床管理体系。<br />
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<div style="font-size: 1.2em; font-weight: bold; letter-spacing: 1.2px;">佩米替尼 (Pemigatinib)</div><br />
<div style="font-size: 0.7em; opacity: 0.85; margin-top: 4px; white-space: nowrap;">达伯坦·Pemazyre·点击展开</div><br />
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<div style="width: 140px; height: 90px; background-color: #f1f5f9; display: flex; align-items: center; justify-content: center; color: #94a3b8; font-size: 0.8em; padding: 10px; text-align: center;">Pemigatinib: Selective inhibition of FGFR1/2/3 kinase</div><br />
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<div style="font-size: 0.8em; color: #64748b; margin-top: 12px; font-weight: 600;">核心靶点：[[FGFR2]]([[融合/重排]])</div><br />
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<th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0; width: 40%;">[[Entrez]]ID</th><br />
<td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">2263([[FGFR2]])</td><br />
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<th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">[[UniProt]]</th><br />
<td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">P21802</td><br />
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<th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">分子量</th><br />
<td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">487.5g/mol</td><br />
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<th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">标准剂量</th><br />
<td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #1e40af;">13.5mg QD (服14停7)</td><br />
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<th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">给药途径</th><br />
<td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">口服 (每日一次)</td><br />
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<td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">[[Incyte]]/[[信达生物]]</td><br />
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<th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569;">药理标志物</th><br />
<td style="padding: 12px; color: #16a34a;">[[高磷血症]]</td><br />
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<h2 style="background: #f1f5f9; color: #0f172a; padding: 10px 18px; border-radius: 0 6px 6px 0; font-size: 1.25em; margin-top: 40px; border-left: 6px solid #0f172a; font-weight: bold;">分子机制：阻断 FGFR 信号轴驱动力</h2><br />
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[[佩米替尼]]的分子药理学核心在于其对变异型 <strong>[[FGFR]]</strong> 激酶活性的深度覆盖。其核心机理如下：<br />
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<li style="margin-bottom: 12px;"><strong>ATP 竞争性抑制：</strong> 佩米替尼以高亲和力结合在 <strong>[[FGFR1]]</strong>、<strong>[[FGFR2]]</strong> 和 <strong>[[FGFR3]]</strong> 激酶结构域的 ATP 结合口袋。通过阻断受体自磷酸化，截断下游 <strong>[[RAS/MAPK]]</strong> 及 <strong>[[PI3K/AKT]]</strong> 信号级联，从而诱导肿瘤细胞生长停滞。</li><br />
<li style="margin-bottom: 12px;"><strong>针对 FGFR2 融合：</strong> 胆管癌中约 10-15% 存在由基因重排形成的融合蛋白（如 [[FGFR2-BICC1]]）。这些融合受体持续活化。[[佩米替尼]]能精准阻断此类异常驱动，展示出对“<strong>[[癌基因成瘾]]</strong>”肿瘤的强效抑制。</li><br />
<li style="margin-bottom: 12px;"><strong>钙磷代谢效应：</strong> 抑制 FGFR 会干扰由 <strong>[[FGF23]]</strong> 调节的肾脏磷排泄。血磷升高是其靶向生效的类效应，临床上作为<strong>[[药效学标志物]]</strong>辅助剂量决策。</li><br />
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<h2 style="background: #f1f5f9; color: #0f172a; padding: 10px 18px; border-radius: 0 6px 6px 0; font-size: 1.25em; margin-top: 40px; border-left: 6px solid #0f172a; font-weight: bold;">FIGHT 系列核心临床研究矩阵</h2><br />
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<th style="padding: 12px; border: 1px solid #cbd5e1; color: #0f172a; width: 25%;">试验代号</th><br />
<th style="padding: 12px; border: 1px solid #cbd5e1; color: #475569;">人群背景/方案</th><br />
<th style="padding: 12px; border: 1px solid #cbd5e1; color: #1e40af;">关键指标获益 (ORR/OS)</th><br />
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<td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">[[FIGHT-202]]</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">含铂化疗进展后的 FGFR2 融合/重排胆管癌。</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;"><strong>客观缓解率 (ORR) 35.5%</strong>；中位 OS 达 17.5个月。奠定全球首个获批地位。</td><br />
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<td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">[[FIGHT-302]]</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">对比一线常规化疗 (GemCis)。</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">探索 FGFR 靶向药在 <strong>[[一线治疗]]</strong> 中的获益，旨在改写临床指南。</td><br />
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<td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">安全性评估</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">长期随访安全性队列。</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">常见副作用为 <strong>[[高磷血症]]</strong> (60%) 及脱发。证实了良好的长期耐受性。</td><br />
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<h2 style="background: #f1f5f9; color: #0f172a; padding: 10px 18px; border-radius: 0 6px 6px 0; font-size: 1.25em; margin-top: 40px; border-left: 6px solid #0f172a; font-weight: bold;">诊疗策略：精准筛选与特异性AE管控</h2><br />
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[[佩米替尼]]的临床实践强调“<strong>[[分子分型指导下的闭环管理]]</strong>”：<br />
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<li style="margin-bottom: 12px;"><strong>伴随诊断筛选：</strong> 启动治疗前必须通过 <strong>[[NGS]]</strong> 或 <strong>[[FISH]]</strong> 确认 <strong>[[FGFR2融合/重排]]</strong> 状态。对于单纯点突变或扩增的胆管癌患者，获益证据相对有限。</li><br />
<li style="margin-bottom: 12px;"><strong>血磷动态监测：</strong> 治疗首周即需开始监测血磷水平。若血磷 > 7.0 mg/dL，应启动 <strong>[[低磷饮食]]</strong> 或加用降磷药物（如司维拉姆），并根据水平进行剂量调节。</li><br />
<li style="margin-bottom: 12px;"><strong>眼科安全性围栏：</strong> 针对 <strong>[[中心性浆液性脉络膜视网膜病变]] (CSR)</strong> 风险，建议在基线及治疗期间定期进行 <strong>[[眼底OCT检查]]</strong>，一旦出现视力异常需立即停药。</li><br />
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<h2 style="background: #f1f5f9; color: #0f172a; padding: 10px 18px; border-radius: 0 6px 6px 0; font-size: 1.25em; margin-top: 40px; border-left: 6px solid #0f172a; font-weight: bold;">关键相关概念</h2><br />
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<li style="margin-bottom: 8px;"><strong>[[FGFR2融合]]：</strong> 肝内胆管癌的核心驱动异变，约占该癌种的 10%-15%。</li><br />
<li style="margin-bottom: 8px;"><strong>[[高磷血症]]：</strong> FGFR 抑制剂最典型的类效应，也是有效靶向抑制的药理指标。</li><br />
<li style="margin-bottom: 8px;"><strong>[[肝内胆管癌]] (iCCA)：</strong> 原发性肝癌的第二大类型，长期缺乏有效的靶向手段。</li><br />
<li style="margin-bottom: 8px;"><strong>[[信达生物]]：</strong> 该药在大中华区的开发合作伙伴，推动了国产 FGFR 靶向药的突破。</li><br />
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<span style="color: #0f172a; font-weight: bold; font-size: 1.05em; display: inline-block; margin-bottom: 15px;">学术参考文献与权威点评</span><br />
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[1] <strong>Abou-Alfa GK, et al. (2020).</strong> <em>Pemigatinib for previously treated, locally advanced or metastatic cholangiocarcinoma (FIGHT-202).</em> <strong>[[The Lancet Oncology]]</strong>.<br><br />
<span style="color: #475569;">[权威点评]：该研究证实了佩米替尼在难治性胆管癌中的卓越疗效，开启了胆道系统肿瘤的精准靶向时代。</span><br />
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[2] <strong>Goyal L, et al. (2023).</strong> <em>Management of FGFR Inhibitor-Related Toxicities.</em> <strong>[[Journal of Clinical Oncology]]</strong>.[Academic Review]<br><br />
<span style="color: #475569;">[学术点评]：详尽综述了以佩米替尼为代表的药物在临床应用中的副作用管控流程，为长期用药安全提供了指南。</span><br />
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佩米替尼 (Pemazyre) 诊疗生态 · 知识图谱<br />
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<td style="width: 85px; background-color: #f8fafc; color: #334155; font-weight: 600; padding: 10px 12px; text-align: right; vertical-align: middle; white-space: nowrap;">关联靶点</td><br />
<td style="padding: 10px 15px; color: #334155;">[[FGFR1]]•[[FGFR2]]•[[FGFR3]]•[[BICC1]]•[[TACC3]]•[[STAT3]]</td><br />
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<td style="width: 85px; background-color: #f8fafc; color: #334155; font-weight: 600; padding: 10px 12px; text-align: right; vertical-align: middle; white-space: nowrap;">直接竞品</td><br />
<td style="padding: 10px 15px; color: #334155;">[[Balversa]]•[[Lytgobi]]•[[Truseltiq]]•[[尼达尼布]]•[[英非拉替尼]]</td><br />
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<td style="width: 85px; background-color: #f8fafc; color: #334155; font-weight: 600; padding: 10px 12px; text-align: right; vertical-align: middle; white-space: nowrap;">战略实体</td><br />
<td style="padding: 10px 15px; color: #334155;">[[Incyte]]•[[信达生物]]•[[SinoCellGene协作]]•[[FDA]]•[[NMPA]]</td><br />
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<td style="width: 85px; background-color: #f8fafc; color: #334155; font-weight: 600; padding: 10px 12px; text-align: right; vertical-align: middle; white-space: nowrap;">研究前沿</td><br />
<td style="padding: 10px 15px; color: #334155;">[[联合PD-1抑制剂]]•[[克服FGFR2网关突变]]•[[耐药ctDNA检测]]•[[术后辅助治疗探索]]</td><br />
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223.160.137.160