Human epidermal growth factor receptor 2(HER2)overexpression and amplification activate key pathways driving tumor progression,leading to HER2-targeted therapies.However,HER2 signaling can also be aberrantly activated...Human epidermal growth factor receptor 2(HER2)overexpression and amplification activate key pathways driving tumor progression,leading to HER2-targeted therapies.However,HER2 signaling can also be aberrantly activated by somatic mutations,independent of overexpression or amplification,contributing to tumorigenesis[1].These mutations,found in domains such as the extracellular(ECD),transmembrane(TMD)/juxtamembrane(JMD),and tyrosine kinase(KD)regions,occur across cancers,from melanoma(1%)to bladder cancer(≤12%)[1,2],suggesting a significant population could benefit from HER2-targeted treatments.Neratinib,an irreversible pan-HER tyrosine kinase inhibitor,has shown efficacy in HER2-mutated cancers and is recommended in National Comprehensive Cancer Network guidelines[3].However,resistance mechanisms,such as secondary HER2 mutations or amplifications,may limit its efficacy[4,5],highlighting the need for combination therapies.展开更多
Human epidermal growth factor receptor 2 (HER2) is a major drug target and clinical biomarker in breast cancertreatment. Targeting HER2 gene amplification is one of the greatest successes in oncology, resulting in the...Human epidermal growth factor receptor 2 (HER2) is a major drug target and clinical biomarker in breast cancertreatment. Targeting HER2 gene amplification is one of the greatest successes in oncology, resulting in the use of awide array of HER2-directed agents in the clinic. The discovery of HER2-activating mutations as novel therapeutictargets in breast and other cancers marked a significant advance in the field, which led to the metastatic breast andother solid tumor trials MutHER (NCT01670877), SUMMIT (NCT01953926), and one arm of plasmaMATCH(NCT03182634). These trials reported initial clinical benefit followed by eventual relapse ascribed to eitherprimary or acquired resistance. These resistance mechanisms are mediated by additional secondary genomicalterations within HER2 itself and via hyperactivation of oncogenic signaling within the downstream signaling axis.展开更多
1文献来源Park JW,Liu MC,Yee D,et al. Adaptive randomization of Neratinib in early breast cancer[J].N Eng J Med,2016,375(1):11-22.2证据水平1b。3背景·肿瘤异质性使确定乳腺癌最佳疗法具有挑战性。·新辅助化疗所能...1文献来源Park JW,Liu MC,Yee D,et al. Adaptive randomization of Neratinib in early breast cancer[J].N Eng J Med,2016,375(1):11-22.2证据水平1b。3背景·肿瘤异质性使确定乳腺癌最佳疗法具有挑战性。·新辅助化疗所能达到的替代终点--病理完全缓解率(pathologic complete response,pCR)成为靶向治疗得以快速发展的重要原因.展开更多
目的:比较吡咯替尼或来那替尼联合卡培他滨(Pyrotinib/Neratinib+Capecitabine,P/N+C)与拉帕替尼联合卡培他滨(Lapatinib+Capecitabine,L+C)治疗HER-2阳性晚期乳腺癌的疗效性及安全性。方法:检索PubM ed、Web of Science、Embase和Cochr...目的:比较吡咯替尼或来那替尼联合卡培他滨(Pyrotinib/Neratinib+Capecitabine,P/N+C)与拉帕替尼联合卡培他滨(Lapatinib+Capecitabine,L+C)治疗HER-2阳性晚期乳腺癌的疗效性及安全性。方法:检索PubM ed、Web of Science、Embase和Cochrane图书馆数据库,选自2005年01月01日截至2021年02月20日的潜在临床研究,合格的研究是前瞻性和注册的临床试验。对无病进展期(progression-free survival,PFS)、客观缓解率(objective response rate,ORR)及疾病控制率(disease control rate,DCR)具有95%置信区间(confidence interval,CI)的合并优势比和治疗相关不良事件的合并风险比进行Meta分析。结果:本次Meta分析包括3项随机对照试验,共有1015例患者被纳入本研究。在P/N+C组,6个月PFS[OR=1.87,95%CI(1.44,2.43),P<0.00001]、12个月PFS[OR=3.87,95%CI(1.95,7.70),P=0.0001]及ORR[OR=1.70,95%CI(1.10,2.64),P=0.02]较L+C组延长;在常见的治疗相关的不良事件中,除P/N+C组的腹泻发生率较L+C组高[RR=3.10,95%CI(1.80,5.35),P<0.0001]以外,其余治疗相关不良事件均无显著差异。结论:本Meta分析表明,使用吡咯替尼或来那替尼联合卡培他滨治疗HER-2阳性晚期乳腺癌的疗效更好,并且是一种安全的治疗选择。展开更多
目的建立HPLC测定来那替尼片含量的方法。方法采Merck Purospher Star RP-18 endcapped色谱柱（4．0mm×250mm，5μm），流动相为磷酸盐缓冲液．甲醇（70：30），流速1．0mL／min，检测波长240nm。结果来那替尼在10．02～120．30μg...目的建立HPLC测定来那替尼片含量的方法。方法采Merck Purospher Star RP-18 endcapped色谱柱（4．0mm×250mm，5μm），流动相为磷酸盐缓冲液．甲醇（70：30），流速1．0mL／min，检测波长240nm。结果来那替尼在10．02～120．30μg/mL浓度范围内线性较好（r=1．0000），平均回收率为99．59％，RSD为0．33％。结论该方法能方便、快速、准确地测定来那替尼片含量。展开更多
基金supported by grants from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute(KHIDI)the Ministry of Health&Welfare,Republic of Korea(grant numbers:HI17C2206 and HA22C0012)+1 种基金Additional support was provided by a grant from the National R&D Program for Cancer Control,National Cancer Center(NCC),Ministry of Health&Welfare,Republic of Korea(grant number:HA22C0052)through the KOSMOS Molecular Tumor Board.
文摘Human epidermal growth factor receptor 2(HER2)overexpression and amplification activate key pathways driving tumor progression,leading to HER2-targeted therapies.However,HER2 signaling can also be aberrantly activated by somatic mutations,independent of overexpression or amplification,contributing to tumorigenesis[1].These mutations,found in domains such as the extracellular(ECD),transmembrane(TMD)/juxtamembrane(JMD),and tyrosine kinase(KD)regions,occur across cancers,from melanoma(1%)to bladder cancer(≤12%)[1,2],suggesting a significant population could benefit from HER2-targeted treatments.Neratinib,an irreversible pan-HER tyrosine kinase inhibitor,has shown efficacy in HER2-mutated cancers and is recommended in National Comprehensive Cancer Network guidelines[3].However,resistance mechanisms,such as secondary HER2 mutations or amplifications,may limit its efficacy[4,5],highlighting the need for combination therapies.
文摘Human epidermal growth factor receptor 2 (HER2) is a major drug target and clinical biomarker in breast cancertreatment. Targeting HER2 gene amplification is one of the greatest successes in oncology, resulting in the use of awide array of HER2-directed agents in the clinic. The discovery of HER2-activating mutations as novel therapeutictargets in breast and other cancers marked a significant advance in the field, which led to the metastatic breast andother solid tumor trials MutHER (NCT01670877), SUMMIT (NCT01953926), and one arm of plasmaMATCH(NCT03182634). These trials reported initial clinical benefit followed by eventual relapse ascribed to eitherprimary or acquired resistance. These resistance mechanisms are mediated by additional secondary genomicalterations within HER2 itself and via hyperactivation of oncogenic signaling within the downstream signaling axis.
文摘1文献来源Park JW,Liu MC,Yee D,et al. Adaptive randomization of Neratinib in early breast cancer[J].N Eng J Med,2016,375(1):11-22.2证据水平1b。3背景·肿瘤异质性使确定乳腺癌最佳疗法具有挑战性。·新辅助化疗所能达到的替代终点--病理完全缓解率(pathologic complete response,pCR)成为靶向治疗得以快速发展的重要原因.
文摘目的:比较吡咯替尼或来那替尼联合卡培他滨(Pyrotinib/Neratinib+Capecitabine,P/N+C)与拉帕替尼联合卡培他滨(Lapatinib+Capecitabine,L+C)治疗HER-2阳性晚期乳腺癌的疗效性及安全性。方法:检索PubM ed、Web of Science、Embase和Cochrane图书馆数据库,选自2005年01月01日截至2021年02月20日的潜在临床研究,合格的研究是前瞻性和注册的临床试验。对无病进展期(progression-free survival,PFS)、客观缓解率(objective response rate,ORR)及疾病控制率(disease control rate,DCR)具有95%置信区间(confidence interval,CI)的合并优势比和治疗相关不良事件的合并风险比进行Meta分析。结果:本次Meta分析包括3项随机对照试验,共有1015例患者被纳入本研究。在P/N+C组,6个月PFS[OR=1.87,95%CI(1.44,2.43),P<0.00001]、12个月PFS[OR=3.87,95%CI(1.95,7.70),P=0.0001]及ORR[OR=1.70,95%CI(1.10,2.64),P=0.02]较L+C组延长;在常见的治疗相关的不良事件中,除P/N+C组的腹泻发生率较L+C组高[RR=3.10,95%CI(1.80,5.35),P<0.0001]以外,其余治疗相关不良事件均无显著差异。结论:本Meta分析表明,使用吡咯替尼或来那替尼联合卡培他滨治疗HER-2阳性晚期乳腺癌的疗效更好,并且是一种安全的治疗选择。
文摘目的建立HPLC测定来那替尼片含量的方法。方法采Merck Purospher Star RP-18 endcapped色谱柱（4．0mm×250mm，5μm），流动相为磷酸盐缓冲液．甲醇（70：30），流速1．0mL／min，检测波长240nm。结果来那替尼在10．02～120．30μg/mL浓度范围内线性较好（r=1．0000），平均回收率为99．59％，RSD为0．33％。结论该方法能方便、快速、准确地测定来那替尼片含量。
