University of California San Francisco Helen Diller Family Comprehensive Cancer Center, 1825 4th St, 3rd Floor BCC, San Francisco, CA, 94158, USA.
Viatris Inc, 1000 Mylan Boulevard, Canonsburg, PA, 15317, USA.
Breast. 2021 Aug;58:18-26. doi: 10.1016/j.breast.2021.03.009. Epub 2021 Apr 1.
Trastuzumab-dkst is a biosimilar of trastuzumab. The phase 3 HERITAGE trial demonstrated equivalent overall response rate (ORR) with trastuzumab-dkst or originator trastuzumab at 24 weeks in patients with HER2-positive metastatic breast cancer receiving chemotherapy. We now present the correlation of ORR with progression-free survival (PFS) for maintenance monotherapy with trastuzumab-dkst vs trastuzumab at 48 weeks of treatment, and the safety, tolerability, and immunogenicity.
HERITAGE is a multicenter, double-blind, randomized, parallel-group, phase 3 study. Patients were randomized 1:1 to receive trastuzumab-dkst or trastuzumab in combination with taxane followed by continued monotherapy until disease progression. The analysis included PFS at 48 weeks to support the primary efficacy endpoint of ORR and safety, tolerability, and immunogenicity of trastuzumab-dkst vs trastuzumab as maintenance monotherapy.
Of 500 randomized patients, 342 entered the monotherapy phase; 214 patients received ≥48 weeks of treatment. There were no statistically significant differences between PFS, ORR, or interim overall survival at week 48 between trastuzumab-dkst and trastuzumab. Week 24 ORR was highly correlated with week 48 PFS (r = 0.75). Cumulative treatment-emergent adverse events (TEAEs) and serious AEs were similar in both groups, with few grade ≥3 TEAEs. Immunogenicity was low and similar in both groups at 48 weeks.
The correlation between ORR and PFS supports the design of first-line metastatic trials assessing biosimilar trastuzumab. Overall, trastuzumab-dkst and trastuzumab were well tolerated with similar efficacy, including ORR and PFS, in combination with a taxane followed by monotherapy.
曲妥珠单抗-dkst 是曲妥珠单抗的生物类似药。III 期 HERITAGE 试验表明，在接受化疗的 HER2 阳性转移性乳腺癌患者中，曲妥珠单抗-dkst 或原研曲妥珠单抗在 24 周时的总缓解率（ORR）等效。我们现在报告了在 48 周治疗时，曲妥珠单抗-dkst 单药维持治疗与曲妥珠单抗相比的 ORR 与无进展生存期（PFS）的相关性，以及安全性、耐受性和免疫原性。
HERITAGE 是一项多中心、双盲、随机、平行组、III 期研究。患者按 1:1 随机接受曲妥珠单抗-dkst 或曲妥珠单抗联合紫杉烷治疗，然后继续单药治疗，直至疾病进展。该分析包括 48 周时的 PFS，以支持 ORR 的主要疗效终点以及曲妥珠单抗-dkst 与曲妥珠单抗作为维持单药治疗的安全性、耐受性和免疫原性。
在 500 名随机患者中，342 名进入单药治疗阶段；214 名患者接受了≥48 周的治疗。在曲妥珠单抗-dkst 与曲妥珠单抗之间，48 周时的 PFS、ORR 或中期总生存期没有统计学上的显著差异。第 24 周的 ORR 与第 48 周的 PFS 高度相关（r=0.75）。两组的累积治疗期间出现的不良事件（TEAEs）和严重不良事件（SAEs）相似，且大多数为 3 级 TEAEs。两组在第 48 周时的免疫原性均较低且相似。
ORR 与 PFS 的相关性支持了评估生物类似物曲妥珠单抗的一线转移性试验的设计。总体而言，曲妥珠单抗-dkst 与曲妥珠单抗联合紫杉烷治疗后单药治疗的耐受性良好，疗效相似，包括 ORR 和 PFS。
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