229例人表皮生长因子受体2阳性Ⅳ期乳腺癌患者曲妥珠单抗的治疗分析

目的探讨曲妥珠单抗对人表皮生长因子受体2(HER2)阳性Ⅳ期乳腺癌的治疗效果及患者预后的影响因素。方法收集229例应用曲妥珠单抗治疗的HER2阳性Ⅳ期乳腺癌患者的临床资料,采用Cox比例风险回归模型分析HER2阳性Ⅳ期乳腺癌患者无进展生存时间(PFS)和总生存时间(OS)的影响因素。结果229例HER2阳性Ⅳ期乳腺癌患者行曲妥珠单抗总体治疗的客观有效率为44.5%,疾病控制率为90.8%,中位PFS为10个月(95%CI:8.748~11.252),中位OS为29个月(95%CI:27.551~30.449)。单因素分析结果显示,激素受体状态和曲妥珠单抗不同线治疗均可能与HER2阳性Ⅳ期乳腺癌的PFS有关,激素受体状态、曲妥珠单抗不同线治疗和进展后是否继续行曲妥珠单抗治疗均可能与HER2阳性Ⅳ期乳腺癌的OS有关(P﹤0.05)。多因素分析结果显示,激素受体状态和曲妥珠单抗不同线治疗是HER2阳性Ⅳ期乳腺癌PFS和OS的独立影响因素(P﹤0.05)。结论一线应用曲妥珠单抗是治疗HER2阳性Ⅳ期乳腺癌的有效手段,在治疗进展后继续应用曲妥珠单抗治疗仍有生存获益。     

曲妥珠单抗一线治疗66例HER2阳性转移性乳腺癌的疗效和安全性分析

摘 要：［目的］ 探讨曲妥珠单抗一线治疗人表皮生长因子受体2（HER2）阳性转移性乳腺癌患者的疗效和安全性。［方法］ 回顾性分析66例曲妥珠单抗联合化疗药物一线治疗HER2阳性转移性乳腺癌患者的临床疗效和不良反应。心脏功能的变化采用彩色超声心动图监测左心室射血分数（LVEF）。 ［结果］ 66例患者中,完全缓解（CR）3例（4.54%）,部分缓解（PR）52例（78.79%）,疾病稳定（SD）9例（13.64%）,疾病进展（PD）2例（3.03%）,客观有效率（ORR）为83.33%（55/66）。中位无进展生存期(mPFS)为12.0个月,中位总生存期（OS）为38.0个月,1、2、3、5、10年生存率为98.5%、80.3%、57.6%、30.3%和11.4%。单因素及多因素分析显示,转移灶的数量是影响PFS的独立因素（P＜0.05）,转移灶的数量、曲妥珠单抗累积使用时间是影响OS的独立因素（均P＜0.05）。曲妥珠单抗治疗相关的不良反应主要表现为心脏功能的下降,最重为3级LVEF下降,发生率为1.5%（1例）。［结论］ 曲妥珠单抗一线治疗HER2阳性转移性乳腺癌患者疗效明显且安全。小负荷转移病灶及早并长期应用曲妥珠单抗治疗,能给患者带来生存获益。     

曲妥珠单抗治疗HER2+乳腺癌的临床进展

临床研究显示曲妥珠单抗与化疗联合用于人表皮生长因子受体2(HER2)+转移性乳腺癌的治疗以及早期乳腺癌的新辅助和辅助治疗,能显著延长患者的生存时间.其与内分泌治疗联合治疗HER2+且雌激素受体阳性的转移性乳腺癌,疗效优于单纯内分泌治疗.曲妥珠单抗联合其他靶向治疗药物,能够逆转肿瘤对曲妥珠单抗的耐药.疾病进展后继续应用曲妥珠单抗仍可使患者生存受益.     

跨线曲妥珠单抗联合不同化疗方案治疗HER2阳性晚期乳腺癌的临床研究

目的 观察跨线曲妥珠单抗联合不同化疗方案治疗人表皮生因子受体2（human epidermal growth factor receptor 2, HER2）阳性晚期乳腺癌的疗效、不良反应和生存期。方法 收集2009年1月至2014年6月间应用跨线曲妥珠单抗（H）联合不同化疗方案治疗HER2阳性的晚期乳腺癌患者71例,均完成一线H治疗,30例患者疾病进展后继续二线H治疗,19例患者疾病再次进展后继续三线H治疗,主要观察疗效、不良反应、生存情况及预后分析。结果 一、二、三线治疗中,曲妥珠单抗联合紫杉类方案和联合非紫杉类方案相比在有效率（RR）和临床获益率（clinical benefit rate, CBR）方面差异均无统计学意义（P＞0.05）。一、二、三线治疗的中位无进展生存时间（PFS）和中位总生存时间（OS）分别为14、9、4月和26、39、53月,总的中位PFS为11月,总的中位OS为36月。一线治疗的PFS较二、三线治疗明显延长（P=0.000）,曲妥珠单抗持续应用至三线的中位OS较仅一线治疗的有延长（P=0.008）。全组患者的1、2、3年生存率分别为88%、66%、39%。71例患者中14例出现了17次心脏相关事件,1例患者因左心室射血分数（LVEF）下降至48%停止曲妥珠单抗治疗,无治疗相关性死亡发生。在OS的Log rank单因素分析中,术后淋巴结转移的个数、有无脑转移、治疗线数、一线治疗的PFS时间与OS有关（P=0.026, P=0.042, P=0.028, P=0.005）。在OS的多因素Cox比例风险模型分析中,治疗线数、有无脑转移、DFS和一线PFS时间为对OS有影响的独立因素（P=0.004,P=0.021, P=0.018, P=0.000）。结论 在HER-2阳性晚期乳腺癌治疗中,疾病进展后跨线曲妥珠单抗联合化疗的疗效优于未继续使用曲妥珠单抗的方案,曲妥珠单抗的跨线使用可以使患者持续获益,跨线曲妥珠单抗联合化疗的方案疗效确切,不良反应可以耐受,值得进一步研究。     

曲妥珠单抗联合内分泌维持治疗HR和HER-2阳性晚期乳腺癌的临床观察

目的 探讨曲妥珠单抗联合内分泌维持治疗激素受体（HR）和人表皮生长因子受体-2（HER-2）阳性复发转移性乳腺癌的疗效与安全性。方法 回顾性分析本院2013年1月至2016年1月收治的HR和HER-2阳性复发转移性乳腺癌患者31例,一线曲妥珠单抗联合化疗达到病情缓解或稳定后继续曲妥珠单抗联合内分泌维持治疗,采用RECIST 1.1版标准评估维持治疗的疗效,采用常见不良反应事件评价标准（CTCAE）4.0版评价毒性反应,根据随访资料分析预后。结果 31例复发转移性乳腺癌维持治疗的中位无进展生存期为12.0个月（95％CI：5.4～18.6个月）。5例患者在一线化疗后获完全缓解,无可评估病灶,其余26例可评估近期疗效,总有效率和临床获益率分别为26.9％和88.5％。内分泌联合曲妥珠单抗的主要不良反应较轻,主要包括乏力（19.4％）、潮热（16.1％）和恶心呕吐（9.7％）。结论 一线曲妥珠单抗联合化疗有效后,曲妥珠单抗联合内分泌维持治疗HR+／HER-2+转移性乳腺癌可进一步改善患者的临床获益,且安全性良好。     

曲妥珠单抗治疗失败的HER-2阳性乳腺癌患者不同后续治疗方案的疗效及影响因素分析

目的:观察人表皮生长因子受体2（human epidermal growth factor receptor-2,HER-2）阳性乳腺癌患者曲妥珠单抗治疗失败后不同后续治疗方案的疗效,分析影响因素。方法:回顾性分析2014年1月至2016年12月在我院肿瘤科治疗的曲妥珠单抗治疗失败的94例HER-2阳性晚期乳腺癌患者,根据其后续治疗方案不同将其分为A组（接受单纯化疗）、B组（接受曲妥珠单抗+化疗）和C组（接受拉帕替尼+化疗）;比较三组患者治疗效果,并分析可能影响抗HER-2治疗效果的相关因素。结果:94例患者均完成随访,中位随访时间22.3个月。三组患者中位无进展生存期（median progression free survival,mPFS）分别为3个月、4.5个月及6个月,差异有统计学意义（P<0.000 1）;C组PFS较A组及B组均明显延长,B组PFS较A组明显延长。A、B、C三组客观有效率（objective response rate,ORR）分别为8.7%、29.7%、38.2%,三组的临床获益率（clinical benefit rate,CBR）分别为21.7%、54.1%、64.7%,以上差异均有统计学意义（P<0.05）。对可能影响PFS的单因素进行分析,拉帕替尼、一线疗程（曲妥珠单抗）获益时间≥6个月、无内脏转移是PFS的影响因素;而拉帕替尼、一线疗程（曲妥珠单抗）获益时间≥6个月是PFS的独立影响因素。结论:对于曲妥珠单抗治疗失败的HER-2阳性晚期乳腺癌患者,后续治疗方案中含抗HER-2靶向药物可改善患者预后。     

转移性乳腺癌曲妥珠单抗一线治疗后进展继续使用曲妥珠单抗的Meta分析

目的:探讨人表皮生长因子受体-2(HER-2)阳性转移性乳腺癌患者在一线接受曲妥珠单抗治疗发生疾病进展后,继续使用曲妥珠单抗的疗效及毒副反应。方法:在Medline、Em-base、Cochrane图书馆、临床试验注册库、中国医院数字化图书馆、万方、维普数据库和美国及欧洲临床肿瘤学会历年会议资料中检索有关HER-2阳性转移性乳腺癌患者,在一线使用含曲妥珠单抗治疗方案发生疾病进展后,再应用曲妥珠单抗的随机对照临床试验(RCT),按Meta分析软件(RevMan 4.2)要求处理有关数据。结果:从1999-2010年共有3个临床实验入选,共625例患者,其中试验组304例,对照组321例。一线接受含曲妥珠单抗治疗后发生疾病进展的HER-2阳性转移性乳腺癌,继用曲妥珠单抗与停用曲妥珠单抗相比,客观缓解率差异有统计学意义,OR=1.62(95%CI为1.08～2.44),P=0.02;临床受益反应率OR=1.57(95%CI为0.78～3.14),P=0.20;无进展生存期/总生存期OR=1.02(95%CI为0.67～1.56),P=0.92;3～4级心脏事件发生率OR=2.39(95%CI为0.61～9.41),P=0.21;腹泻发生率OR=1.60(95%CI为1.10～2.32),P=0.01。结论:对于一线接受含曲妥珠单抗方案后发生疾病进展的HER-2阳性转移性乳腺癌患者,继续使用曲妥珠单抗可显著提高客观缓解率,但对临床受益反应率以及无进展生存期/总生存期无明显改善;且继续使用曲妥珠单抗增加了腹泻的发生率,但对增加心脏毒性作用无统计学意义。     

曲妥珠单抗耐药的机制和对策研究进展

曲妥珠单抗是人表皮生长因子受体2(HER2)过表达乳腺癌患者的重要治疗手段之一.但即使是HER2高表达或是基因扩增的患者,曲妥珠单抗单药的有效率也仅为12%～34%,中位缓解期约9个月,许多患者在接受治疗的12个月内出现疾病进展.对曲妥珠单抗的耐药机制进行研究,有助于我们为曲妥珠单抗耐药的患者寻找新的治疗药物和方法.     

曲妥珠单抗治疗转移性乳腺癌研究进展

人源性抗HER2单抗—曲妥珠单抗（trastuzumab）是第一个针对HER2阳性转移性乳腺癌病人进行癌基因靶向治疗的药物，于1998年9月被FDA批准上市。曲妥珠单抗静脉输注后，抗体靶向性作用于HER2受体过度表达的肿瘤细胞，具有显著的临床疗效且不良反应较小。     

曲妥珠单抗联合含长春瑞滨方案治疗人表皮生长因子受体2阳性晚期乳腺癌的研究

目的观察曲妥珠单抗联合长春瑞滨方案治疗人表皮生长因子受体2（HER-2）阳性晚期乳腺癌的疗效及安全性。方法收集中国医学科学院肿瘤医院2001年2月至2012年2月期间应用曲妥珠单抗联合含长春瑞滨化疗方案治疗的55例晚期乳腺癌患者的临床资料。回顾性分析其临床特点、药物疗效、不良反应及生存状况。结果应用曲妥珠单抗联合含长春瑞滨方案治疗的55例患者中,完全缓解（CR）2例,部分缓解（PR）24例,疾病稳定（SD）16例,疾病进展（PD）13例,总有效率为47.3%,疾病控制率为76.4%,中位PFS为8.0个月。患者中位生存时间为46.1个月,1年生存率为95.8%,2年生存率为76.8%,5年生存率为45.7%。3例心悸考虑为曲妥珠单抗相关的不良反应,患者未出现明显心功能不全。不良反应主要为化疗药物导致的血液学毒性和非血液学毒性。结论曲妥珠单抗联合含长春瑞滨方案治疗HER-2阳性的晚期乳腺癌疗效肯定,毒性可耐受。     

Trastuzumab-based Retreatment after Lapatinib in Heavily Pretreated HER2 Positive Metastatic Breast Cancer: an Anatolian Society of Medical Oncology Study

Background: For HER2 positive metastatic breast cancer (MBC), continuing anti-HER2 therapy beyondprogression is associated with improved outcome. However retreatment with trastuzumab after lapatinibprogression is controversial. We retrospectively analyzed the efficacy of trastuzumab-based chemotherapy inHER2+ metastatic breast cancer patients whose disease progressed after lapatinib. Materials and Methods:Between October 2010 and May 2013, 54 patients whose disease progressed after lapatinib were retreated withtrastuzumab-based chemotherapy. Efficacy and toxicity results were evaluated retrospectively. Results: Themedian age of patients was 46 (range 27-67). Fourteen patients (26%) had metastases at the time of diagnosis.All of the patients had received trastuzumab in an adjuvant or metastatic setting, while 16 (30%) had receivedtwo lines of trastuzumab. All patients had received lapatinib plus capecitabine. The median chemotherapyline for the metastatic setting was 2 (range 1-7). Cranial metastases were identified in 27 (50%) patients. 53patients received trastuzumab-based chemotherapy following lapatinib progression while one patient receivedtrastuzumab monotherapy. Combination chemotherapy consisted of navelbin (n=33), taxane (n=10), gemcitabine(n=2), platinum (n=2) and platinum with taxane (n=6). The median treatment cycle was 5 (range 1-44). Among 49patients assessed for response 2 (4%) showed CR, 12 (25%) PR, 11 (22%) SD and 24 (49%) disease progression.Asymptomatic cardiotoxicity was reported in 2 (4%) of the patients. At a median follow-up of 9 months (1-39),median progression-free survival was 5 months (95% CI 4.1-5.9) and median overall survival was 10 months(95% CI 6.9-13.0). PFS and OS were not affected by the absence/presence of cranial metastases. Conclusions:Retreatment with trastuzumab-based therapy after lapatinib progression showed efficacy in heavily treatedMBC patients.     

Prolonged survival of patients receiving trastuzumab beyond disease progression for HER2 overexpressing metastatic breast cancer (MBC)

BACKGROUND: The aim of this retrospective analysis was to evaluate the impact of trastuzumab-based regimens on the survival of patients with HER2-overexpressing metastatic breast cancer (MBC). The study specifically focussed on the influence of the continuation of trastuzumab-based treatment despite tumor progression on survival. PATIENTS AND METHODS: Patients with HER2 overexpressing MBC were included in this retrospective analysis. HER2 overexpression was determined by the immunohistochemical staining score (DAKO Hercep Test). Trastuzumab was applied at a loading dose of 4 mg/kg and a maintenance dose of 2 mg/kg. RESULTS: Among 136 HER2 overexpressing patients (DAKO score 3+), 66 patients received first-line trastuzumab, 47 patients received trastuzumab as second-line therapy and 23 patients received trastuzumab beyond disease progression. There was no significant difference regarding the duration of trastuzumab-based treatment (first-line: 29.5 weeks vs. second-line: 25 weeks). Moreover, there was no difference in the response rate (first-line: 37.9% vs. second-line: 35.7%) or the median survival (p = 0.47 log rank). Patients who received = 2 trastuzumab-based regimens for MBC survived significantly longer compared to those who had received only 1 regimen (= 2 regimens: 62.4 months vs. 1 regimen: 38.5 months; p = 0.01 log rank). CONCLUSIONS: Trastuzumab is highly effective in the treatment of HER2 overexpressing MBC. Compared to historical controls, overall survival appears to be markedly prolonged, particularly in patients who received sequential trastuzumab-based treatment beyond disease progression.     

Trastuzumab treatment in multiple lines: current data and future directions

Trastuzumab improves response rate, time to progression, and overall survival when combined with first-line chemotherapy in patients with human epidermal growth factor receptor 2-positive (HER2-positive) metastatic breast cancer (MBC). However, the benefits of continuing trastuzumab beyond disease progression have not been clearly established. The literature was reviewed to obtain data on trastuzumab use beyond disease progression. In general, data from retrospective and observational studies suggest that there may be clinical benefit when trastuzumab is used beyond disease progression. These results are supported by prospective non-randomized studies. Response rates and survival outcomes have generally been superior in patients who have continued trastuzumab after disease progression compared with those who have not. Moreover, recent data from two prospective randomized phase III trials have shown that adding trastuzumab to the treatment regimen in patients with MBC who have progressed on trastuzumab-based therapy significantly prolongs progression-free survival. Emerging evidence from randomized controlled trials supports the potential clinical utility of continuing trastuzumab-based therapy beyond progression and supports the National Comprehensive Cancer Network recommendation to consider this treatment approach. Future treatment of HER2-positive MBC may involve trastuzumab being used in successive regimens in combination with other targeted therapies.     

Retreatment with trastuzumab-based therapy after disease progression following lapatinib in HER2-positive metastatic breast cancer

BackgroundPreclinical data suggest that treatment with lapatinib reinduces sensitivity to trastuzumab in human epidermal growth factor receptor 2(HER2)-positive breast cancer cells.Patients and methodsBetween January 2007 and November 2010, 179 HER2-positive metastatic breast cancer patients were treated with lapatinib and capecitabine at nine Italian institutions. We evaluated the clinical outcome of 69 patients (38.5%) retreated with trastuzumab after lapatinib progression.ResultsVisceral metastases were identified in 51 (74%) and brain metastases in 16 patients (23%). All patients were pretreated with both trastuzumab- and lapatinib-based therapy. We observed with retreatment with trastuzumab-based therapy: 1 complete remission (2%), 18 partial remission (29%) and 10 stable disease ≥6 months (14%) and 47% of clinical benefit (CB). Median duration of response was 8.1 months [95% confidence interval (CI) 5.5–10.7]. No unexpected toxic effects occurred. At a median follow-up of 13 months, median progression-free survival was 4.9 months (95% CI 4.2–5.6) and overall survival (OS) 19.4 months (95% CI 14.0–25.0). Median OS was longer for patients experiencing CB (not reached versus 13.4 months for patients without CB, P = 0.002). Brain involvement was associated with lower median OS (17.3 versus 23.3 months for patients without brain disease; P = 0.021).ConclusionRetreatment with trastuzumab-based therapy showed CB in 47% of patients progressing during lapatinib-based therapy, leading to a prolonged OS.     

Weekly Gemcitabine and Trastuzumab in the Treatment of Patients With HER2-Overexpressing Metastatic Breast Cancer

BackgroundThe use of trastuzumab in combination with either a taxane or vinorelbine has improved the efficacy of treatment for women with HER2-positive (HER+) breast cancer. We investigated the activity and toxicity of the gemcitabine/trastuzumab combination as first- or second-line treatment in women with HER2+ metastatic breast cancer (MBC).Patients and MethodsForty-one women with HER2+ MBC were treated with gemcitabine 1000 mg/m² intravenously (I.V.) days 1, 8, and 15 and trastuzumab 4-mg/kg I.V. loading dose and then 2 mg/kg weekly. Cycles were repeated every 28 days. Patients were evaluated after 8 weeks of treatment; responders/stable patients continued treatment until progression.ResultsPatients received a median of 28 weeks of treatment. Eleven of 37 evaluable patients (30%; 95% CI, 17%–46%) had major responses. The median progression-free survival (PFS) was 4 months (95% CI, 1.9–5.3 months), with a 1-year PFS of 17%. Four of 15 patients (27%) who had previously received trastuzumab for MBC had partial responses. The gemcitabine/trastuzumab combination was well tolerated.ConclusionThe combination of gemcitabine and trastuzumab is an active regimen but appears less active than trastuzumab in combination with either taxanes or vinorelbine. The role of gemcitabine/trastuzumab (versus gemcitabine alone) in women who have already received a trastuzumab-containing regimen for HER2+ MBC is not defined by this study.     

Trastuzumab Retreatment after Relapse on Adjuvant Trastuzumab Therapy for Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer: Final Results of the Retreatment after Herceptin Adjuvant Trial

AimsTrastuzumab, in combination with chemotherapy, is the standard of care for patients with early and metastatic human epidermal growth factor receptor 2 (HER2)-positive breast cancer. The Retreatment after HErceptin Adjuvant trial assessed the efficacy and safety of trastuzumab plus a taxane as first-line treatment for patients with metastatic breast cancer (MBC) who had relapsed after adjuvant trastuzumab for HER2-positive early breast cancer.Materials and methodsIn total, 43 patients with HER2-positive MBC who had received previous adjuvant trastuzumab for ≥10 months, with a relapse-free interval of ≥6 months after the last adjuvant trastuzumab dose, were recruited. Eligible patients (n = 41) were assigned to receive trastuzumab, either weekly or every 3 weeks, in combination with docetaxel or paclitaxel until disease progression.ResultsAt the final analysis, with a median follow-up time of 40 months, a positive response was observed in 25/41 patients (61%; 95% confidence interval: 48.7–80.4%), stable disease in 7/41 (17.1%) and progressive disease in 6/41 (14.6%). Three patients had missing response assessments (one had no measurable lesions at baseline and two had no post-baseline tumour assessments). The median progression-free survival (PFS) was 8.0 months (95% confidence interval: 6–11 months) and the median overall survival was 25.0 months (16–33 months). No correlation was found between response rate, PFS or overall survival and the duration of adjuvant trastuzumab treatment, trastuzumab-free interval, relapse-free interval, hormone receptor status or type of pre-metastatic treatment. The most common adverse events (all grades) were alopecia (32%) and diarrhoea (32%). Six patients (14.6%) developed at least one serious adverse event. No congestive heart failure or any unexpected adverse events were reported.ConclusionTrastuzumab, in combination with a taxane, is an effective and well-tolerated first-line treatment for MBC in patients who relapse after trastuzumab-based adjuvant therapy.     

Retrospective evaluation of clinical outcomes in patients with HER2-positive advanced breast cancer progressing on trastuzumab-based therapy in the pre-lapatinib era

BackgroundPatients with HER2-positive breast cancer whose disease has become resistant to the anti-HER2 monoclonal antibody trastuzumab can benefit from lapatinib, a dual epidermal growth factor receptor/HER2 tyrosine kinase (TK) inhibitor. Before the availability of this compound, trastuzumab was often continued beyond disease progression, usually in addition to further chemotherapy, an approach which was not based on randomized studies. We sought to retrospectively compare the clinical outcomes of patients who, upon progression during an initial trastuzumab-based regimen, stopped or continued trastuzumab in addition to further chemotherapy.Patients and MethodsFrom the clinical records of 407 patients with HER2-positive advanced breast cancer, we identified 279 patients progressing during an initial trastuzumab-based treatment. Of these patients, 83 continued trastuzumab in addition to chemotherapy, and 112 received chemotherapy alone.ResultsWe found no difference in response rate (28% vs. 30%; P = .5), median time to second tumor progression (8.4 months vs. 7 months; P = .24), or median postprogression survival (20.6 months and 15.4 months; P = .29) according to whether patients continued or stopped trastuzumab. At multivariate analysis, continuation of trastuzumab was associated with a statistically insignificant trend toward reduced risk of second progression (hazard ratio, 0.753; P = .08).ConclusionPatients with HER2-positive advanced breast cancer developing tumor progression during an initial trastuzumab-based regimen did not seem to benefit significantly from the continuation of trastuzumab in addition to chemotherapy. For these patients, there is evidence from a large randomized trial that effective HER2 targeting can be accomplished by inhibiting the HER2 TK activity with lapatinib.     

Use of trastuzumab beyond disease progression: observations from a retrospective review of case histories

HER2 overexpression is associated with poor breast cancer prognosis and is the target for the humanized monoclonal antibody trastuzumab. This novel agent, when administered until disease progression in combination with chemotherapy, extends the survival of women with HER2-positive metastatic breast cancer (MBC). However, the optimal duration of trastuzumab therapy remains to be confirmed. We conducted a retrospective case review study of women with HER2-positive MBC who continued to receive trastuzumab beyond disease progression. Objectives were to assess whether treatment beyond disease progression shows any evidence of efficacy and to evaluate the feasibility of this approach. One hundred five patients (median age, 47 years; range, 24-77 years) were identified in 13 centers. Women had received /=1 more trastuzumab regimen. Trastuzumab treatment beyond progression appears to be of value, producing responses and clinical benefit, and is well tolerated without significant cardiac toxicity. The feasibility of this approach warrants examination in prospective trials.     

Time to first tumor progression as a predictor of efficacy of continued treatment with trastuzumab beyond progression in human epidermal growth factor receptor 2-positive metastatic breast cancer

Background  

Trastuzumab demonstrates significant clinical benefits in HER2-positive metastatic breast cancer (MBC), and recent clinical trials suggest that trastuzumab should be continued in combination with other chemotherapy beyond progression. There is an urgent need to assess if patients could substantially benefit from continuing trastuzumab-based therapy.     

Safety and efficacy study of oral metronomic vinorelbine combined with trastuzumab (mNH) in HER2-positive metastatic breast cancer: a phase II trial

Purpose

We conducted a single-arm prospective phase II trial to evaluate the efficacy and safety of oral metronomic vinorelbine combined with trastuzumab (mNH) in human epidermal growth factor receptor 2-positive (HER2-positive) metastatic breast cancer (MBC) patients.

Methods

HER2-positive MBC patients received oral vinorelbine 40 mg thrice a week and trastuzumab (loading dose of 8 mg/kg, followed by 6 mg/kg every 3 weeks) until disease progression, unacceptable toxicity, or consent withdrawal. The primary endpoints were objective response rate (ORR), clinical benefit rate (CBR; CR?+?PR?+?SD for?≥?24 weeks). The secondary endpoints were progression-free survival (PFS), tolerability, and overall survival (OS).

Results

Twenty patients with HER2-positive MBC were enrolled, with a median of 1 prior chemotherapy regimens for MBC. Median age was 61.5 years (95% Confidence Interval (CI) 48.6–63.1). Visceral involvements presented in 14 patients (70.0%). ORR was 20.0%, and CBR was 75% with 4 PR (20.0%) and 11 SD (55.0%). The median PFS (mPFS) and median OS (mOS) were 7.4 months (95% CI 3.2–11.5) and 45.8 months (95%CI: not reached), respectively. The mPFS was 17.7 months (95%CI not reached) and 5.8 months (95%CI 5.6–5.9) in mNH as first-line and?≥?second-line therapy (log rank p?=?0.03), respectively. The most common grade 1 adverse events (AEs) included nausea (15%), leukopenia (15%), ALT/AST elevation (15%), diarrhea (10%), and peripheral neuropathy (10%). Grade 2 adverse events included leukopenia (5%) and neutropenia (10%). No grade 3/4 AEs were observed.

Conclusions

Oral metronomic vinorelbine combined with trastuzumab is a well-tolerated and effective anti-tumor regimen for HER2-positive MBC.