Efficacy, patterns of use and cost of Pertuzumab in the treatment of HER2+ metastatic breast cancer in Singapore: The National Cancer Centre Singapore experience

BACKGROUND Pertuzumab is a humanized anti-human epidermal growth factor receptor 2(HER2)monoclonal antibody found in a Phase III clinical trial to significantly improve median survival in HER2 positive metastatic breast cancer(MBC)when used in combination with a taxane and Trastuzumab,and its clinical efficacy has transformed the therapeutic landscape of HER2-positive breast cancer.There are currently few reports on the pattern of use and value of Pertuzumab in real world settings.Our study describes the clinical efficacy and treatment costs of Pertuzumab in HER2-positive MBC treated in a tertiary cancer centre in Singapore in a predominantly Asian population.AIM To investigate the clinical efficacy and treatment costs of Pertuzumab in HER2-positive MBC in an Asian population in Singapore.METHODS A retrospective study of 304 HER2-positive MBC patients seen at National Cancer Centre Singapore between 2011-2017 was conducted.Demographic and clinical data were extracted from electronic medical records.Clinical characteristics and billing data of patients who received Pertuzumab were compared with those who did not.RESULTS Thirty-one(62.0%)of the fifty(16.4%)patients who received Pertuzumab as firstline therapy.With a median follow-up of 21.5 mo,there was a statistically significant difference in the median overall survival between Pertuzumab and non-Pertuzumab groups[51.5(95%CI:35.8–60.0)vs 32.9(95%CI:28.1–37.5)mo;P=0.0128].Two(4.88%)patients in the Pertuzumab group experienced grade 3(G3)cardiotoxicity.The median treatment cost incurred for total chemotherapy for the Pertuzumab group was 130456 Singapore Dollars compared to 34523 Singapore Dollars for the non-Pertuzumab group.The median percentage of total chemotherapy costs per patient in the Pertuzumab group spent on Pertuzumab was 50.3%.CONCLUSION This study shows that Pertuzumab use in the treatment of metastatic breast cancer is associated with a significantly better survival and a low incidence of serious cardiotoxicity.However,the proportionate cost of Pertuzumab therapy remains high and further cost-effectiveness studies should be conducted.

HER2阳性乳腺癌新辅助治疗策略和现状

乳腺癌新辅助治疗是指在手术前进行的全身药物治疗。人表皮生长因子受体2(HER2)阳性乳腺癌预后不良,新辅助治疗为HER2阳性乳腺癌的治疗提供了新型模式,已经彻底改变了其治疗方式和预后。目前曲妥珠单抗和帕妥珠单抗双重抗HER2靶向联合非蒽环类化疗是首选的较高病理完全缓解率(pCR)以及更好预后的新辅助方案之一。未来曲妥珠单抗联合小分子TKI药物,以及新的ADC类药物,免疫治疗联合靶向治疗等,结合可靠生物标志物后,将实现HER2阳性乳腺癌更为精准的治疗。本文就双靶时代的HER2阳性乳腺癌新辅助治疗进行简要综述,并对其未来发展方向进行展望。

Pyrotinib is effective in both trastuzumab-sensitive and primary resistant HER2-positive breast tumors

Objective: Primary resistance to trastuzumab frequently occurs in human epidermal growth factor receptor 2(HER2)-positive(+) breast cancer patients and remains a clinical challenge. Pyrotinib is a novel tyrosine kinase inhibitor that has shown efficacy in the treatment of HER2+ breast cancer. However, the efficacy of pyrotinib in HER2+ breast cancer with primary trastuzumab resistance is unknown.Methods: HER2+ breast cancer cells sensitive or primarily resistant to trastuzumab were treated with trastuzumab, pyrotinib, or the combination. Cell proliferation, migration, invasion, and HER2 downstream signal pathways were analyzed. The effects of pyrotinib plus trastuzumab and pertuzumab plus trastuzumab were compared in breast cancer cells in vitro and a xenograft mouse model with primary resistance to trastuzumab.Results: Pyrotinib had a therapeutic effect on trastuzumab-sensitive HER2+ breast cancer cells by inhibiting phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT) and rat sarcoma virus(RAS)/rapidly accelerated fibrosarcoma(RAF)/mitogen-activated protein kinase(MAPK)/extracellular-signal regulated kinase(ERK)pathways. In primary trastuzumab-resistant cells, pyrotinib inhibited cell growth, migration, invasion, and HER2 downstream pathways, whereas trastuzumab had no effects. The combination with trastuzumab did not show increased effects compared with pyrotinib alone. Compared with pertuzumab plus trastuzumab, pyrotinib plus trastuzumab was more effective in inhibiting cell proliferation and HER2 downstream pathways in breast cancer cells and tumor growth in a trastuzumab-resistant HER2+ breast cancer xenograft model.Conclusions: Pyrotinib-containing treatments exhibited anti-cancer effects in HER2+ breast cancer cells sensitive and with primary resistance to trastuzumab. Notably, pyrotinib plus trastuzumab was more effective than trastuzumab plus pertuzumab in inhibiting tumor growth and HER2 downstream pathways in HER2+ breast cancer with primary resistance to trastuzumab. These findings support clinical testing of the therapeutic efficacy of dual anti-HER2 treatment combining an intracellular small molecule with an extracellular antibody.

TAC化疗方案联合西妥昔单抗、帕妥珠单抗治疗HER2阳性乳腺癌的效果观察

目的:观察TAC化疗方案(多西他赛^(+)多柔比星^(+)环磷酰胺)联合西妥昔单抗、帕妥珠单抗治疗人表皮生长因子受体2(HER2)阳性乳腺癌的效果。方法:选取2020年4月—2021年12月甘肃省人民医院收治的HER2阳性乳腺癌患者68例作为研究对象,采用随机数字表法分成观察组与对照组,各34例。对照组采用TAC化疗方案治疗,观察组在对照组基础上采用西妥昔单抗、帕妥珠单抗双靶向治疗。比较两组治疗效果、免疫功能、新生血管指标。结果:观察组治疗总有效率高于对照组,差异有统计学意义(P=0.028)。治疗前,两组CD3^(+)、CD4^(+)、CD4^(+)/CD8^(+)水平比较,差异无统计学意义(P>0.05);治疗后,两组CD3^(+)、CD4^(+)、CD4^(+)/CD8^(+)水平降低,观察组高于对照组,差异有统计学意义(P<0.05)。治疗前,两组三叶因子1(TFF1)、人类泛素偶联酶E2C(UBE2C)水平比较,差异无统计学意义(P>0.05);治疗后,两组TFF1、UBE2C水平降低,观察组低于对照组,差异有统计学意义(P<0.05)。结论:TAC化疗方案联合西妥昔单抗、帕妥珠单抗治疗HER2阳性乳腺癌的应用效果显著,可改善免疫功能及血管生成指标。

Pertuzumab in combination with trastuzumab and chemotherapy for Chinese patients with HER2-positive metastatic gastric or gastroesophageal junction cancer:a subpopulation analysis of the JACOB trial

Background:The JACOB trial(NCT01774786)was a double-blinded,placebo-controlled,randomized,multicenter,international,phase III trial evaluating the efficacy and safety of adding pertuzumab to trastuzumab and chemo-therapy in first-line treatment of human epidermal growth factor receptor 2(HER2)-positive metastatic gastric cancer/gastroesophageal junction cancer(GEJC).The aim of this analysis was to investigate efficacy and safety outcomes in the Chinese subpopulation from the JACOB trial.Methods:This post hoc subpopulation analysis included all patients recruited in China's Mainland(n=163;20.9%)between June 2013 and January 2016.The patients were randomly assigned in a 1:1 ratio to receive pertuzumab plus trastuzumab and chemotherapy(pertuzumab group;n=82)or placebo plus trastuzumab and chemotherapy(con-trol group;n=81).Intravenous pertuzumab(840 mg)and trastuzumab(8 mg/kg loading and 6 mg/kg maintenance doses)were given every 3 weeks until disease progression or unacceptable toxicity.Chemotherapy was given as per standard regimens/doses of capecitabine or 5-fluorouracil plus cisplatin.The primary endpoint was overall survival(OS);secondary efficacy endpoints included progression-free survival(PFS),and overall objective response rate(ORR).Results:The median OS was 18.7 months in the pertuzumab group and 16.1 months in the control group(hazard ratio[HR]0.75;95%confidence interval[CI]0.49 to 1.14).The median PFS was 10.5 and 8.6 months in the pertuzumab and control groups,respectively(HR 0.85;95%CI 0.60 to 1.21),and the median ORRs were 68.9%and 55.7%,respectively.The treatment effect in this Chinese subpopulation showed consistency with that in the global ITT population with numerically lower HR for OS and PFS compared with the control group.The safety profiles of the pertuzumab and control groups in this Chinese subpopulation analysis were generally comparable.The most common grade 3-5adverse events were neutropenia,anemia,and leukopenia.However,due to the nature of being a post hoc subgroup analysis,the results presented here are descriptive only and need to be interpreted with caution.Conclusions:OS and PFS were numerically improved by adding pertuzumab to trastuzumab and chemotherapy as first-line treatment in Chinese HER2-positive gastric cancer/GEJC patients,and this regimen demonstrated an acceptable safety profile.

人表皮生长因子受体2与临床病理特征及新辅助化疗病理完全缓解相关性研究

目的探讨人表皮生长因子受体2(HER2)蛋白表达水平与临床病理特征以及HER2阳性型乳腺癌抗HER2靶向药联合新辅助化疗疗效的相关性。方法回顾性分析2019年7月至2023年7月161例HER2阳性型乳腺癌行曲妥珠单抗和帕妥珠单抗联合新辅助化疗患者的临床病理资料,统计分析HER2蛋白表达水平和患者确诊时年龄、月经状态、肿瘤大小、淋巴结转移情况、雌激素受体(ER)、孕激素受体(PR)、Ki67等临床病理特征的相关性,以及HER2蛋白表达水平和其他临床病理特征与患者接受靶向联合新辅助化疗后病理完全缓解(pCR)的相关性。结果161例患者中,80例患者达到了pCR,81例患者未达到pCR。ER(χ2=21.239,P<0.001)、PR(χ2=23.733,P<0.001)与HER2蛋白表达水平有关联。HER2蛋白表达水平(χ2=19.940,P<0.001)、ER(χ2=26.328,P<0.001)与pCR率有关联。多因素分析结果显示,ER、PR阴性的患者HER2蛋白表达水平更高(ER:O^R=0.157,95%CI:0.030~0.837,P=0.030;PR:O^R=0.234,95%CI:0.065~0.841,P=0.026);HER2蛋白表达水平为ICH(3+)的患者pCR率更高(O^R=6.393,95%CI:1.469~20.885,P=0.016);ER阴性的患者有更高的pCR率(O^R=0.381,95%CI:0.160~0.910,P=0.030)。结论HER2蛋白表达水平与激素受体有相关性,HER2蛋白表达水平对HER2阳性型乳腺癌患者行靶向药物联合新辅助化疗的疗效预测有重要意义,此外,雌激素受体也是影响新辅助疗效的重要因素。

曲妥珠单抗与帕妥珠单抗双靶治疗在人表皮生长因子受体-2阳性乳腺癌新辅助治疗中的应用效果

目的探讨并分析曲妥珠单抗联合帕妥珠单抗治疗方案在人表皮生长因子受体-2阳性乳腺癌新辅助治疗中的应用效果。方法选取2019年4月至2022年6月福建医科大学附属漳州市医院收治的52例人表皮生长因子受体-2阳性乳腺癌患者展开研究,遵循随机数字表法分组原则,将其分成观察组与对照组,各26例,予以对照组紫杉醇、卡铂和曲妥珠单抗疗法,予以观察组曲妥珠单抗与帕妥珠单抗双靶治疗,将两组治疗效果进行比较。结果观察组治疗有效率88.46%高于对照组65.39%(P<0.05)。观察组术后病理缓解率96.15%高于对照组65.38%(P<0.05);且观察组病理完全缓解率高达50.00%,高于对照组26.92%(P<0.05)。治疗前,对比两组患者生活质量各维度的评分差异无统计学意义(P>0.05);治疗后,两组生活质量各个维度评分均有所提高,其中观察组各维度的评分高于对照组(P<0.05)。观察组不良反应发生率26.92%与对照组不良反应发生率30.77%对比差异无统计学意义(P>0.05)。结论人表皮生长因子受体-2阳性乳腺癌中通过曲妥珠单抗与帕妥珠单抗双靶治疗的临床疗效显著,不仅能够有效提高病理缓解率,还有助于患者生活质量的提升,同时也不会增加不良反应,可以作为新辅助治疗中的新思路应用于临床。

帕妥珠单抗联合TP新辅助化疗方案对HER2阳性乳腺癌患者的影响分析

目的:探讨帕妥珠单抗联合紫杉类和铂类药物(TP)新辅助化疗方案对人表皮生长因子受体2(HER2)阳性乳腺癌患者免疫功能的影响及安全性分析.方法:选取2021年1月—2023年1月成武县人民医院收治的HER2阳性乳腺癌患者80例为研究对象,随机分为对照组和观察组,各40例.对照组采用TP新辅助化疗方案治疗,观察组在对照组基础上联合帕妥珠单抗治疗.比较两组治疗效果.结果:观察组肿瘤控制率高于对照组,差异有统计学意义(P=0.045);治疗后,两组CD4^(+)、CD4^(+)/CD8^(+)水平高于治疗前,CD8^(+)水平低于治疗前,且观察组优于对照组,差异有统计学意义(P<0.05);治疗后,两组半胱氨酸天冬氨酸蛋白酶-3、生存素水平均降低,且观察组低于对照组,差异有统计学意义(P<0.05);两组不良反应发生率比较,差异无统计学意义(P>0.05).结论:帕妥珠单抗联合TP新辅助化疗方案治疗HER2阳性乳腺癌有较好的肿瘤控制率,能改善机体免疫功能,调节乳腺组织凋亡分子平衡,且不会增加不良反应发生率.

曲妥珠单抗与帕妥珠单抗双靶向联合化疗药物在人表皮生长因子受体2阳性乳腺癌新辅助治疗中的效果以及影响因素

目的分析曲妥珠单抗与帕妥珠单抗双靶向联合化疗药物(紫杉类+卡铂)在人表皮生长因子受体2(HER-2)阳性乳腺癌新辅助治疗中的效果以及影响因素。方法收集2020年6月1日至2022年3月31日在首都医科大学附属北京妇产医院乳腺科诊断为HER-2阳性的Ⅰ~Ⅲ期乳腺癌的41例女性患者的临床资料进行回顾性分析。观察临床疗效,评估新辅助治疗后手术切除标本的病理学完全缓解(pCR)状态并通过残余肿瘤负荷分级评估病理疗效,评价用药安全性;分析影响新辅助治疗后pCR的相关因素。结果41例患者临床总缓解率为90.2%(37/41),病理有效率为78.0%(32/41)。未出现严重不良事件。单因素分析结果显示淋巴结转移、组织学分级、脉管癌栓、孕激素受体、激素受体水平是影响pCR的相关因素,差异均有统计学意义(均P<0.05)。多因素分析结果显示,激素受体阳性(比值比=5.625)、高组织学分级(比值比=4.278)、淋巴结转移(比值比=7.333)及脉管癌栓(比值比=6.000)是影响HER-2阳性乳腺癌患者新辅助治疗后pCR的独立危险因素(均P<0.05)。结论曲妥珠单抗与帕妥珠单抗双靶向联合化疗药物新辅助治疗HER-2阳性乳腺癌患者效果显著,激素受体阳性、高组织学分级、淋巴结转移与脉管癌栓是影响pCR的独立危险因素。

白蛋白紫杉醇联合曲妥珠单抗及帕妥珠单抗对人表皮生长因子受体2阳性乳腺癌患者的疗效

目的:探讨白蛋白紫杉醇联合曲妥珠单抗及帕妥珠单抗治疗人表皮生长因子受体2(HER2)阳性的晚期乳腺癌(ABC)患者的疗效。方法:选取60例HER2阳性ABC患者为研究对象,根据不同治疗方式,将其分为对照组(n=30)和观察组(n=30)。对照组采用多西他赛联合曲妥珠单抗、帕妥珠单抗治疗;观察组采用白蛋白紫杉醇联合曲妥珠单抗、帕妥珠单抗治疗。两组患者均治疗6个周期(以21 d为1个周期)。比较两组患者临床疗效、生存期、肿瘤标志物水平和不良反应发生情况。结果:观察组客观有效率(ORR)、临床获益率(CBR)均高于对照组(P<0.05)。治疗后,两组患者糖类抗原(CA)15-3、癌胚抗原(CEA)、CA125水平均降低(P<0.05),且观察组低于对照组(P<0.05);两组患者CA15-3、CEA水平差异均为高效应[95%CI:1.142(4.347~11.533)、1.485(1.900~3.941)],CA125水平差异为中效应[95%CI:0.670(0.652,5.048)]。观察组无进展生存期(PFS)、总生存期(OS)均高于照组(P<0.05);两组患者PFS、OS水平差异均为弱效应[95%CI:-2.760(-4.892~3.366)、-3.604(-5.813~4.353)]。两组患者不良反应发生率无统计学差异(P>0.05)。结论:白蛋白紫杉醇联合曲妥珠单抗及帕妥珠单抗治疗HER2阳性ABC患者具有明显疗效,可调节肿瘤标志物分泌,延长患者生存期,且具有一定安全性。

289例单克隆抗体抗肿瘤药品不良反应报告分析

目的分析单克隆抗体类抗肿瘤药品不良反应(ADR)发生的一般规律和特点,为临床合理用药提供依据。方法收集陕西省2016年1月1日至2020年12月31日各级医疗卫生机构上报至陕西省食品药品检验研究院的289例单抗类抗肿瘤ADR报告,从性别、年龄、给药途径、药品种类、临床转归和ADR的临床表现进行分析。结果收集的ADR报告中共涉及5种抗肿瘤药,ADR发生主要以40岁以上人群居多(92.04%),女性人数大于男性。在289例ADR报告中临床表现为309例次,以血液系统最为常见,其次为消化系统、全身性系统、皮肤及其附件损伤。不同的单抗类抗肿瘤药引起的ADR有相似点,即骨髓抑制均占较高比例。不同的是,贝伐珠单抗、曲妥珠单抗消化道症状出现较多;西妥昔单抗、帕妥珠单抗皮肤毒性明显;利妥昔单抗则是易出现寒战高热。5种抗肿瘤药均以静脉滴注给药为主,但仍有11例静脉推注或胸膜腔内给药。引起严重的ADR最多的是利妥昔单抗(34例),其ADR主要表现为骨髓抑制和高热。其次为贝伐珠单抗(27例),其ADR主要表现为骨髓抑制。在转归方面,痊愈和好转占86.51%。另有1例结肠癌老年女性患者使用贝伐珠单抗20 d后出现结肠穿孔,1月后死亡。结论单抗类抗肿瘤ADR的发生与患者年龄、给药途径、药物种类等密切关联,使用存在一些特殊的用法及注意事项,使用时应注意。应充分了解患者病情以及该类药物特点,按时监测患者生理指标,以减少或避免ADR的发生,最大程度利用单克隆抗体抗肿瘤药的优势。

人表皮生长因子受体2阳性乳腺癌应用新辅助治疗的疗效及影响因素分析

目的分析人表皮生长因子受体2(HER2)阳性乳腺癌应用新辅助治疗的疗效及影响因素。方法选取47例HER2阳性乳腺癌患者,均接受曲妥珠单抗和帕妥珠单抗联合紫杉类+卡铂新辅助治疗。比较不同激素受体(HR)表达情况乳腺癌患者的临床特征,HER2阳性乳腺癌患者新辅助治疗总病理学完全缓解(tpCR)的影响因素采用Logistic回归分析。结果47例HER2阳性乳腺癌患者中,HR阴性19例,HR阳性28例,HR阳性患者年龄≤50岁、月经状态为绝经前比例均明显高于HR阴性患者,乳腺病理学完全缓解(bpCR)率、tpCR率和客观缓解率(ORR)均明显低于HR阴性患者,差异均有统计学意义(P﹤0.01)。47例接受曲妥珠单抗和帕妥珠单抗联合紫杉类+卡铂新辅助治疗患者的tpCR率为70.21%(33/47),单因素分析结果显示,HER2阳性乳腺癌患者新辅助治疗的tpCR可能与雌激素受体(ER)和孕激素受体(PR)表达状态有关(P﹤0.01);多因素Logistic回归分析结果显示,ER表达情况、PR表达情况均不是HER2阳性乳腺癌患者新辅助治疗tpCR的影响因素(P﹥0.05)。结论曲妥珠单抗和帕妥珠单抗联合紫杉类+卡铂新辅助治疗HER2阳性乳腺癌的效果较好,分层分析显示,HR阴性患者较HR阳性患者更容易在新辅助治疗后达到病理学完全缓解。对于ER、PR阳性同时HER2阳性乳腺癌患者应寻找更有效的治疗靶点以提高治疗效果。

两种不同新辅助化疗方案联合双靶对HER-2阳性乳腺癌病理完全缓解率的影响

目的探讨不同新辅助化疗方案联合曲妥珠单抗(H)和帕妥珠单抗(P)对HER-2阳性乳腺癌病理完全缓解(pCR)率的影响及安全性并分析获得pCR的影响因素。方法回顾性分析2019年5月至2021年5月我院使用AC-THP或TCbHP新辅助治疗(NAT)且完成手术的HER-2阳性乳腺癌患者临床病理资料,主要研究终点是总病理完全缓解(tpCR)率及不良反应,次要终点是乳房病理完全缓解(bpCR)率和腋窝病理完全缓解(apCR)率,并分析影响tpCR的因素。结果128例患者纳入分析,其中75例使用TCbHP方案,53例使用AC-THP方案。总tpCR率为60.9%,其中TCbHP为62.7%,AC-THP为58.5%(χ^(2)=0.228,P=0.633);总bpCR率为64.1%,TCbHP为65.3%,AC-THP为62.3%(χ^(2)=0.127,P=0.721);总apCR率为70.3%,TCbHP为78.7%,AC-THP为58.5%,差异有统计学意义(χ^(2)=6.009,P=0.014)。单因素分析显示,激素受体(HR)状态、雌激素受体(ER)表达、孕激素受体(PR)表达、HER-2状态、腋窝淋巴结状态、临床分期及紫杉类药物种类是影响tpCR的相关因素。多因素分析发现,ER表达情况、HER-2状态、腋窝淋巴结状态是预测tpCR的独立因素。两方案总体不良反应可控,但TCbHP方案的3~4级血液毒性反应更高。结论TCbHP方案的tpCR率、apCR率、bpCR率均要高于AC-THP方案,但仅在apCR上观察到统计学差异。两种方案的安全性良好。ER阴性、HER-2(3+)、腋窝淋巴结阴性患者的tpCR率更高。

曲妥珠单抗结合帕妥珠单抗治疗HER2阳性乳腺癌的疗效及对血清miR-375 miR-30d表达变化的影响

目的:观察曲妥珠单抗联合帕妥珠单抗治疗人表皮生长因子受体-2(HER2)阳性乳腺癌的疗效及血清微RNA-375(miR-375)、微RNA-30 d(miR-30d)表达量变化的影响。方法:采用简单随机数字表及随机数余数分组法将2020年2月至2023年2月我院收治的139例HER2阳性乳腺癌患者分为联合组(n=70,曲妥珠单抗联合帕妥珠单抗治疗)与对照组(n=69,曲妥珠单抗治疗),每隔21d给药1次为1个疗程,共治疗4个疗程。比较两组临床疗效,比较治疗前、治疗后两组肿瘤相关指标[糖类抗原(CA125、CA153)、癌胚抗原(CEA)、循环肿瘤细胞(CTC)]、T淋巴细胞亚群(CD3^(+)、CD4^(+)、CD8^(+)、CD4^(+)/CD8^(+))、血清微RNA(miR-375、miR-30d)表达量及生活质量[癌症患者生命质量测定量表(QLQ-C30)]水平变化,并统计两组不良反应。结果:治疗期间两组均无患者死亡。联合组临床总有效率高于对照组(P<0.05);治疗后,两组血清CA125、CA153、CEA、CTC阳性率、CD8^(+)、miR-375、miR-30d表达量、QLQ-C30评分均低于治疗前(P<0.05),血清CD3^(+)、CD4^(+)、CD4^(+)/CD8^(+)水平均高于治疗前,联合组各项指标差值均高于对照组(P<0.05);所有不良反应经对症处理后均缓解,联合组心悸发生率高于对照组(P<0.05)。结论:曲妥珠单抗联合帕妥珠单抗能有效提高HER2阳性乳腺癌患者免疫功能,降低肿瘤标志物水平及miR-375、miR-30d表达,改善生活质量,且安全性较高,临床疗效显著。

曲妥珠单抗与帕妥珠单抗联合化疗在HER2阳性乳腺癌患者辅助治疗中的安全性分析

目的 探究曲妥珠单抗与帕妥珠单抗联合化疗应用于人类表皮生长因子受体2(HER2)阳性乳腺癌患者辅助治疗中的安全性。方法 回顾性分析80例HER2阳性乳腺癌患者的临床资料,所有患者均给予TCbHP方案[曲妥珠单抗(H)+帕妥珠单抗(P)联合多西他赛(T)+卡铂(Cb)]进行辅助治疗。分析患者毒副反应发生情况。结果 所有患者均按计划完成全部治疗,超声心动图监测未出现左心室射血分数(LVEF)降低超过基线10%的现象。80例患者恶心呕吐、骨髓抑制、乏力、心悸、皮疹瘙痒、失眠、骨骼肌肉疼痛、手足麻木、腹泻、便秘发生率分别为60.0%、30.0%、71.3%、5.0%、12.5%、27.5%、55.0%、30.0%、27.5%、16.3%。其中3级恶心呕吐10例、3级骨髓抑制8例,乏力、心悸、皮疹瘙痒、失眠、骨骼肌肉疼痛、手足麻木、腹泻、便秘均为1~2级。结论 曲妥珠单抗、帕妥珠单抗联合多西他赛和卡铂用于HER2阳性乳腺癌患者的辅助治疗, 3级以上严重毒副反应发生率低、安全可控。

1例帕妥珠单抗联合曲妥珠单抗治疗致4级腹泻的药学实践

目的:分析1例乳腺癌患者术后使用帕妥珠单抗注射液联合注射用曲妥珠单抗辅助治疗出现4级腹泻后的用药情况。方法:临床药师参与1例乳腺癌患者术后使用帕妥珠单抗注射液联合注射用曲妥珠单抗辅助治疗出现4级腹泻的临床治疗,协助医生制定止泻方案,并对患者进行药学监护。结果:临床药师参与后,成功控制了患者的4级腹泻。结论:临床药师通过参与乳腺癌患者术后使用帕妥珠单抗注射液联合注射用曲妥珠单抗辅助治疗所致4级腹泻的临床治疗,提供个体化用药方案,发挥了积极作用。

Her-2阳性转移性乳腺癌的生物靶向治疗

目的:回顾性分析本院2010年至2012年Her-2阳性转移性乳腺癌患者的治疗经验,评价在曲妥珠单抗联合紫杉醇治疗的基础上联合与不联合帕妥珠单抗的疗效。方法:设定一定的入选及排除标准,筛选出符合要求的病例进行分析。采用曲妥珠单抗+帕妥珠单抗联合紫杉醇治疗的患者为观察组(54例),曲妥珠单抗+紫杉醇治疗的患者为对照组(71例),比较2种治疗方法的疗效。结果:相比于曲妥珠单抗+紫杉醇,曲妥珠单抗+帕妥珠单抗联合紫杉醇治疗在肿瘤缓解率及肿瘤无进展生存期方面具有明显优势,差异有统计学意义(P<0.05)。结论:曲妥珠单抗+帕妥珠单抗联合紫杉醇治疗Her-2阳性转移性乳腺癌疗效更好,值得临床推广。

HER2 therapies and gastric cancer:A step forward

Gastric cancer usually is diagnosed in advanced stages and thus current medical practice affords limited therapeutic options.However,recent studies established the role of human epidermal growth factor receptor 2(HER2)in clinical management.Trastuzumab,an antiHER2 monoclonal antibody,acquired a main role in advanced gastric cancer harboring HER2 overexpression and/or amplification improving survival to 17.1 mo according to trastuzumab for gastric cancer phaseⅢtrial results.Also,new promising drugs,such as c-Met inhibitors,are in development and assessment for this setting.Certainly,novel drugs will emerge in the next feel years for help oncologists improve clinical management of advanced gastric cancer providing higher survival and quality of life.In this mini-review we will discuss some issues in this regard and provide an actual overview of this setting.

Personalizing therapies for gastric cancer: Molecular mechanisms and novel targeted therapies

Globally,gastric cancer is the 4thmost frequently diagnosed cancer and the 2ndleading cause of death from cancer,with an estimated 990000 new cases and738000 deaths registered in 2008.In the advanced setting,standard chemotherapies protocols acquired an important role since last decades in prolong survival.Moreover,recent advances in molecular therapies provided a new interesting weapon to treat advanced gastric cancer through anti-human epidermal growth factor receptor 2(HER2)therapies.Trastuzumab,an anti-HER2 monoclonal antibody,was the first target drug in the metastatic setting that showed benefit in overall survival when in association with platinum-5-fluorouracil based chemotherapy.Further,HER2 overexpression analysis acquired a main role in predict response for trastuzumab in this field.Thus,we conducted a review that will discuss the main points concerning trastuzumab and HER2 in gastric cancer,providing a comprehensive overview of molecular mechanisms and novel trials involved.