Department of Internal Medicine, Hematology and Medical Oncology Ward, Cancer Research Center, Cancer Institute, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran.
Department of Internal Medicine, School of Medicine, Kerman University of Medical Sciences, Kerman, Iran.
BMC Pharmacol Toxicol. 2022 Jul 28;23(1):57. doi: 10.1186/s40360-022-00599-x.
This study compared efficacy and safety of TA4415V, a trastuzumab biosimilar, with reference trastuzumab in patients with human epidermal growth factor receptor 2-positive (HER2-positive) early-stage breast cancer treated in the neoadjuvant setting in Iran.
Patients were randomly assigned to receive neoadjuvant TA4415V or reference trastuzumab concurrently with docetaxel (TH phase) for 4 cycles after treatment with 4 cycles of doxorubicin and cyclophosphamide (AC phase). Chemotherapy was followed by surgery. The primary endpoint was the comparison of pathologic complete response (pCR) rate in the per-protocol population. Secondary endpoints included comparisons of overall response rate (ORR), breast-conserving surgery (BCS), safety, and immunogenicity.
Ninety-two participants were analyzed in the per-protocol population (TA4415V, n = 48; reference trastuzumab, n = 44). The pCR rates were 37.50% and 34.09% with TA4415V and reference drug, respectively. The 95% CI of the estimated treatment outcome difference (- 0·03 [95% CI - 0.23 to 0.16]) was within the non-inferiority margin. No statistically significant difference was observed between the groups for other efficacy variables in the ITT population: ORR (89.13% vs. 83.33%; p = 0.72) and BCS (20.37% vs. 12.96%; p = 0.42) in the TA4415V and reference drug group, respectively. At least one grade 3 or 4 adverse events occurred in 27 (50%) patients in the TA4415V group versus 29 (53.70%) in the reference trastuzumab group (p = 0.70). The decrease in left ventricular ejection fraction (LVEF), as an adverse event of special interest (AESI) for trastuzumab, was compared between treatment groups in TH phase. Results demonstrated an LVEF decrease in 7 (12.96%) and 9 (16.67%) patients in TA4415V and reference trastuzumab groups, respectively (p = 0.59). Anti-drug antibodies (ADA) were not detected in any samples of groups.
Non-inferiority for efficacy was demonstrated between TA4415V and Herceptin based on the ratio of pCR rates in HER2-positive early breast cancer patients. In addition, ORR and BCS, as secondary endpoints, were not significantly different. Safety profile and immunogenicity were also comparable between the two groups.
本研究比较了 TA4415V（曲妥珠单抗生物类似药）与参考曲妥珠单抗在伊朗新辅助治疗中用于人表皮生长因子受体 2 阳性（HER2 阳性）早期乳腺癌患者的疗效和安全性。
患者随机分配接受新辅助 TA4415V 或参考曲妥珠单抗，同时接受多西他赛（TH 期）治疗 4 个周期，继以多柔比星和环磷酰胺（AC 期）治疗 4 个周期。化疗后行手术。主要终点为意向治疗人群中病理完全缓解（pCR）率的比较。次要终点包括总缓解率（ORR）、保乳手术（BCS）、安全性和免疫原性的比较。
在方案人群（TA4415V，n=48；参考曲妥珠单抗，n=44）中分析了 92 名参与者。TA4415V 和参考药物的 pCR 率分别为 37.50%和 34.09%。治疗结局差异的估计 95%CI（-0.03 [95%CI -0.23 至 0.16]）在非劣效性边界内。在 ITT 人群中，两组之间其他疗效变量无统计学差异：ORR（89.13% vs. 83.33%；p=0.72）和 BCS（20.37% vs. 12.96%；p=0.42）分别在 TA4415V 和参考药物组。TA4415V 组至少有 1 例 3 级或 4 级不良事件的患者为 27 例（50%），参考曲妥珠单抗组为 29 例（53.70%）（p=0.70）。曲妥珠单抗的左心室射血分数（LVEF）下降（一种特殊关注的不良事件，AESI）作为一种不良事件，在 TH 期被比较了治疗组之间的差异。结果显示，TA4415V 组和参考曲妥珠单抗组分别有 7 例（12.96%）和 9 例（16.67%）患者的 LVEF 下降（p=0.59）。两组均未检测到抗药物抗体（ADA）。
基于 HER2 阳性早期乳腺癌患者 pCR 率的比值，TA4415V 与赫赛汀的疗效相当，证明了非劣效性。此外，ORR 和 BCS 作为次要终点，无显著差异。两组的安全性和免疫原性也相当。
