van Ramshorst Mette S, van Werkhoven Erik, Honkoop Aafke H, Dezentjé Vincent O, Oving Irma M, Mandjes Ingrid A, Kemper Inge, Smorenburg Carolien H, Stouthard Jacqueline M, Linn Sabine C, Sonke Gabe S
Department of Medical Oncology, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
Department of Biometrics, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
Breast. 2016 Oct;29:153-9. doi: 10.1016/j.breast.2016.07.017. Epub 2016 Aug 5.
The addition of pertuzumab to neoadjuvant trastuzumab-based chemotherapy improves pathologic complete response rates in HER2-positive breast cancer. However, increased toxicity has been reported with the addition of pertuzumab, and this may differ between various chemotherapy backbone regimens. We evaluated toxicities of pertuzumab when added to either FEC-T (5-fluorouracil, epirubicin, cyclophosphamide, trastuzumab) or weekly paclitaxel, trastuzumab, carboplatin (PTC).
The TRAIN-2 study is a neoadjuvant randomized controlled trial in stage II and III HER2-positive breast cancer (NCT01996267). Patients are randomly assigned to receive either three cycles of FEC-T plus pertuzumab or three cycles of PTC plus pertuzumab, followed by six cycles of PTC plus pertuzumab in both arms. Toxicities are described per treatment arm according to the Common Toxicity Criteria for Adverse Events version 4.03.
This analysis includes 110 patients balanced over both treatment arms. Neutropenia was the most common hematologic toxicity, with grade 3-4 occurring in 53% in the FEC-T-arm and in 51% in the PTC-arm. Febrile neutropenia occurred in 9% in the FEC-T arm and did not occur in the PTC-arm. Secondary G-CSF prophylaxis was used in 35-40% of patients. Asymptomatic ejection fraction decrease grade 2 was observed in 24% in the FEC-T-arm and 11% in the PTC-arm. The most common grade 3-4 non-hematologic toxicity was diarrhea (5% in the FEC-T-arm and 18% in the PTC-arm).
Pertuzumab in combination with FEC-T mostly causes neutropenia, and when added to PTC mostly causes diarrhea. Significant cardiac toxicity is rare with both regimens, and toxicity is overall well manageable.
在以曲妥珠单抗为基础的新辅助化疗中加入帕妥珠单抗可提高HER2阳性乳腺癌的病理完全缓解率。然而，有报道称添加帕妥珠单抗会增加毒性，且在不同的化疗主干方案中可能有所不同。我们评估了帕妥珠单抗分别添加到FEC-T（5-氟尿嘧啶、表柔比星、环磷酰胺、曲妥珠单抗）或每周紫杉醇、曲妥珠单抗、卡铂（PTC）方案中的毒性。
TRAIN-2研究是一项针对II期和III期HER2阳性乳腺癌的新辅助随机对照试验（NCT01996267）。患者被随机分配接受三个周期的FEC-T加帕妥珠单抗或三个周期的PTC加帕妥珠单抗，随后两组均接受六个周期的PTC加帕妥珠单抗。根据不良事件通用毒性标准第4.03版描述每个治疗组的毒性。
该分析纳入了110例在两个治疗组中分布均衡的患者。中性粒细胞减少是最常见的血液学毒性，FEC-T组3-4级发生率为53%，PTC组为51%。FEC-T组发热性中性粒细胞减少发生率为9%，PTC组未发生。35%-40%的患者使用了二级粒细胞集落刺激因子预防性治疗。FEC-T组24%的患者出现无症状的2级射血分数下降，PTC组为11%。最常见的3-4级非血液学毒性是腹泻（FEC-T组为5%，PTC组为18%）。
帕妥珠单抗联合FEC-T主要导致中性粒细胞减少，添加到PTC中则主要导致腹泻。两种方案中严重心脏毒性均罕见，总体毒性易于管理。
