曲妥珠单抗、卡铂及多西他赛联合治疗乳腺癌的疗效及安全性评价

目的 探讨曲妥珠单抗、卡铂及多西他赛联合治疗HER-2阳性乳腺癌的疗效及安全性.方法 选取收治的90例HER-2阳性乳腺癌患者为研究对象,按随机分组法将所有患者分为观察组和对照组,每组各45例.对照组采用多西他赛联合卡铂治疗,观察组采用曲妥珠单抗、卡铂及多西他赛联合治疗.比较两组患者临床疗效及不良反应发生率.结果 观察组临床总有效率(73.3%)显著高于对照组(51.1%)(P<0.05).观察组的病理疗效(62.2%)显著高于对照组(40.0%)(P<0.05).两组患者的贫血、骨髓抑制、恶心呕吐及肝功能损害等不良反应发生率无统计学意义(P>0.05).治疗后,观察组的HMGI-C阳性率和CRP水平显著低于对照组(P<0.05).结论 曲妥珠单抗、卡铂及多西他赛联合治疗HER-2阳性乳腺癌的疗效显著,可有效降低HMGI-C阳性率和CRP水平,值得在临床推广.     

Dual HER2 blockade in the first-line treatment of metastatic breast cancer - A retrospective population-based observational study in Danish patients

ObjectivesRandomized clinical trials do not include a population that truly reflects a real-world population, due to their inclusion and exclusion criteria. This leads to concerns about the applicability of these studies in a clinical practice. In the present study, we aim to describe the clinical and demographic characteristics, treatment patterns, and clinical outcomes in a population of patients with HER2-positive metastatic breast cancer who received pertuzumab and trastuzumab as first-line treatment in a real-world setting.MethodsThe database of the Danish Breast Cancer Group was used to assemble data on patients included in the period April 2013 to August 2017. The primary endpoints were overall survival (OS) and progression-free survival (PFS).ResultsA cohort of 291 patients with a median age of 58 years was registered. Hereof 112 (38%) patients with de novo disease (primary disseminated) and 179 (62%) with recurrence. The median follow-up for OS was 24.1 months. The median OS was 41.8 months (95% CI, 37.7 to NE) and the median PFS was 15.8 months (95% CI, 14.0 to 19.9). For de novo patients alone, the median OS was not reached whereas the median PFS was 17.9 months (95% CI, 14.3 to 27.3).Hazard ratios for patients receiving vinorelbine showed comparable results as for the whole population.ConclusionThis heterogeneous patient population in a real-world setting had a PFS comparable with what could be expected from the related randomized trial. The de novo patients had better OS and PFS as compared to patients with recurrence.     

Prognosis of pregnancy after breast cancer diagnosis according to the type of treatment: A population-based study in Korea by the SMARTSHIP group

BackgroundsIn this study, we evaluated the incidence and outcomes of pregnancy after breast cancer was diagnosed in women of childbearing age. Additionally, we evaluated the prognosis of patients who became pregnant after breast cancer, according to the treatment.MethodsThis was a retrospective cohort study of women aged 20–45 years who were surgically treated for breast cancer between 2004 and 2014 using the Korean National Health Insurance database. The patients were classified into six groups according to the treatment. Propensity score matching was applied to the cohort to analyze the risk of breast cancer-associated mortality after pregnancy and childbirth.ResultsOf the 45,765 patients who had been newly diagnosed with breast cancer, 1826 (4%) became pregnant after breast cancer diagnosis. Among the pregnant group, the HR of the risk of death was 0.15 (95% CI, 0.06 to 0.36) for patients who became pregnant ≥49 months after the diagnosis. In patients who received endocrine therapy and chemotherapy, the pregnant group had better prognosis than the non-pregnant group. There was no significant difference between the pregnant group and the non-pregnant group in patients who received chemotherapy and trastuzumab with or without endocrine therapy.ConclusionThe risk of death was low in women who became pregnant ≥49 months after the diagnosis of breast cancer. The prognosis of pregnant women was non-inferior to that of non-pregnant women, even in women who received trastuzumab. These findings provide reassurance to patients with HER2-positive cancer who are considering future pregnancy.     

Trastuzumab and Hypofractionated Whole Breast Radiotherapy: A Victorious Combination?

Introduction

The purpose of this study was to examine the impact of trastuzumab on acute skin and cardiac toxicity in patients with breast cancer treated with chemotherapy with or without trastuzumab and adjuvant whole breast hypofractionated radiotherapy (hypo-RT).

胃癌靶向药物治疗进展

胃癌是消化系统常见的恶性肿瘤之一,由于早诊率低,大多数患者在诊断时已经处于疾病中晚期。化疗是进展期胃癌的重要治疗方法,但是,细胞毒性药物联合方案并没有从根本上提高化疗有效率。分子靶向治疗是近年来在治疗血液系统肿瘤和实体瘤中涌现出的新治疗手段。随着对胃癌发生、发展和转移过程中分子生物学机制的研究,这种治疗手段也逐步应用于胃癌治疗的临床实践。这些靶向治疗策略主要包括:HER2单克隆抗体,表皮生长因子受体抑制剂,血管生成抑制剂,多靶点酪氨酸激酶抑制剂,细胞周期蛋白依赖性激酶(CDKs),mTOR抑制剂,c-Met抑制剂,基质金属蛋白酶抑制剂,IGF-1R抑制剂,HSP90抑制剂等。本文就进展期胃癌近年来分子靶向治疗的研究结果及相关进展作一综述。     

An exploratory analysis of the factors leading to delays in cancer drug reimbursement in the European Union: The trastuzumab case

BackgroundThe European Union (EU) has adopted a common procedure for granting marketing authorisation for cancer drugs. Nevertheless, pricing and reimbursement decisions are a competency of EU national governments, and their policies are diverse. We aimed to evaluate the time for trastuzumab reimbursement approval and its association to health expenditure, to health policy performance, to the availability of cost-effectiveness studies and to breast cancer outcome.MethodsBreast cancer outcome was estimated by the mortality/incidence (M/I) ratio. Trastuzumab reimbursement approval dates were provided by Roche. Spearman’s rank correlation and Wilcoxon rank-sum test were used to evaluate associations and/or differences between the variables studied. Additional analyses were made by grouping countries according to compliance to the 180 day timeframe stipulated in the EU 89/105/EEC Directive for drug pricing and reimbursement.ResultsA statistically significant inverse and strong correlation between breast cancer M/I ratio and health expenditure (r_s = –0.730, p < 0.001) and health policy performance (r_s = –0.711, p < 0.001) was found, meaning the better the score and the higher the expenditure, the fewer patients died after a breast cancer diagnosis. Factors associated with trastuzumab faster reimbursement and compliance to the 89/105/EEC Directive were better health policy score, higher health expenditure and availability of cost-effectiveness studies.ConclusionHigher health policy scores and health expenditure are associated with faster reimbursement of trastuzumab and better breast cancer outcome. Although the study design does not allow inference of causal associations, a marked difference is observed between Eastern and Western Europe, with long delays and increased breast cancer mortality identified in Eastern European countries.     

Trastuzumab versus lapatinib: The cardiac side of the story

HER2 gene plays a pivotal role in the pathogenesis of 20% of breast cancer patients. At the same time, it is one of the main cardiac survival pathways when subjected to bio-mechanical stress including exposure to anthracyclines. With the emergence of the anti-HER2 targeting agents, concerns raised regarding the potential cardiac toxicities of these drugs. In the early clinical trials with trastuzumab, it was evident that it has a significant cardiac toxicity. The incidence of symptomatic heart failure ranged from 4% to 7% with trastuzumab alone, and 27% when administered concurrently with doxorubicin. On the other hand, available data suggest that lapatinib is much less cardiotoxic. The incidence of symptomatic heart failure has been constantly reported to be less than 0.5%. In this review, we discuss the possible theories behind the differences in the cardiac profile of both agents. We emphasize on the role of cardiac bioenergetics and the effects of trastuzumab and lapatinib on ATP production through the different effects they exert on the cardiac mitochondria.     

Trastuzumab Emtansine in HER2+ Recurrent Metastatic Non–Small-Cell Lung Cancer: Study Protocol

The treatment outcome has been unsatisfactory for patients with non–small-cell lung cancer (NSCLC) refractory to standard first-line chemotherapy. Trastuzumab emtansine (T-DM1), an anti-HER2 antibody conjugated with a vinca alkaloid, has been approved for clinical use in HER2+ breast cancer in many countries. Approximately 5% of NSCLC tumors possess HER2 alterations, and T-DM1 has shown excellent antitumor effects against HER2+ lung cancer cell lines in preclinical models. Therefore, we hypothesized that T-DM1 could significantly inhibit the growth of HER2+ lung cancers. We have launched a nonrandomized phase II trial of T-DM1 monotherapy for patients with HER2+ lung cancers. The major eligibility criteria are as follows: age ≥ 20 years, pathologically diagnosed NSCLC with documented HER2 positivity (immunohistochemistry 3+, both immunohistochemistry 2+ and fluorescence in situ hybridization positive, or exon 20 insertion mutation), and previous chemotherapy. Thirty patients will receive T-DM1 3.6 mg/kg every 3 weeks. The primary endpoint is the overall response rate. This trial will provide information on whether T-DM1 monotherapy is effective against HER2+ lung cancer.