Ntekim Atara I, Ibraheem Abiola, Sofoluwe Adenike A, Kotila Olayinka, Babalola Chinedum, Karrison Theodore, Olopade Christopher O
Department of Radiation Oncology, College of Medicine, University of Ibadan, Ibadan, Nigeria.
Section of Hematology Oncology, University of Chicago, Chicago, IL.
JCO Glob Oncol. 2020 Jul;6:983-990. doi: 10.1200/GO.20.00043.
Human epidermal growth factor receptor 2 (HER2) subtype of breast cancer is aggressive, leading to a poor outcome. Targeted therapy with trastuzumab has been shown to be effective in the treatment of HER2-positive breast cancer. Cardiotoxicity is a specific adverse effect associated with trastuzumab. The initial formulation of trastuzumab was intravenous, but presently, a subcutaneous formulation (Herceptin SC) is available. Insufficient data on the response rate and cardiotoxic effects of trastuzumab among indigenous Black populations exist. In all studies evaluating the efficacy and toxicity of trastuzumab alone or in combination with chemotherapy, indigenous Black populations in Africa were not included, yet they are the ones most likely to benefit from highly effective cancer medicines. This is partly due to poor oncology clinical trial infrastructure in sub-Saharan Africa. The ARETTA study protocol (ClinicalTrials.gov identifier: NCT03879577) is a phase II multicenter feasibility study to evaluate the efficacy and toxicity of docetaxel given every 3 weeks for 4 cycles plus trastuzumab in 60 previously untreated women with nonmetastatic breast cancer. The primary endpoint is to assess the proportion of patients with complete pathologic response. Secondary endpoints include the number of patients who require dose delays in docetaxel and trastuzumab attributed to hematologic, GI, and cardiac toxicity. Pharmacokinetic profiles of subcutaneous trastuzumab will also be determined. The ARETTA study will provide important information on the clinical response and cardiac safety of subcutaneous trastuzumab in combination with docetaxel among indigenous African women with nonmetastatic breast cancer. It can also be used as a blueprint for conducting biomarker-driven oncology clinical trials in low-resource settings such as sub-Saharan Africa.
乳腺癌的人表皮生长因子受体2(HER2)亚型侵袭性强,预后较差。已证明曲妥珠单抗靶向治疗对HER2阳性乳腺癌有效。心脏毒性是与曲妥珠单抗相关的一种特殊不良反应。曲妥珠单抗最初的剂型是静脉注射剂,但目前有皮下注射剂型(赫赛汀皮下注射剂)。关于非洲本土黑人人群中曲妥珠单抗的缓解率和心脏毒性作用的数据不足。在所有评估曲妥珠单抗单药或联合化疗疗效和毒性的研究中,未纳入非洲本土黑人人群,然而他们最有可能从高效抗癌药物中获益。部分原因是撒哈拉以南非洲地区肿瘤学临床试验基础设施薄弱。ARETTA研究方案(ClinicalTrials.gov标识符:NCT03879577)是一项II期多中心可行性研究,旨在评估每3周给予多西他赛共4个周期联合曲妥珠单抗对60例既往未接受治疗的非转移性乳腺癌女性患者的疗效和毒性。主要终点是评估达到完全病理缓解的患者比例。次要终点包括因血液学、胃肠道和心脏毒性而需要延迟多西他赛和曲妥珠单抗剂量的患者数量。还将测定皮下注射曲妥珠单抗的药代动力学特征。ARETTA研究将为皮下注射曲妥珠单抗联合多西他赛治疗非洲本土非转移性乳腺癌女性患者的临床反应和心脏安全性提供重要信息。它还可作为在撒哈拉以南非洲等资源匮乏地区开展生物标志物驱动的肿瘤学临床试验的蓝本。