Background

PF-05280014 was compared with trastuzumab sourced from the European Union (trastuzumab-EU), each plus paclitaxel, as first-line treatment for human epidermal growth factor receptor 2-positive metastatic breast cancer in a phase III study. Equivalence between treatment groups was demonstrated.

Objective

The aim of this study was to report long-term safety and overall survival (OS) over 6 years after the first patient was screened.

Patients and methods

Randomized patients received intravenous PF-05280014 or trastuzumab-EU, each plus paclitaxel, until objective disease progression. OS, long-term safety, subgroup safety (patients ongoing after day 378), and time-to-treatment discontinuation (TTD) were assessed based on the final statistical analysis plan amended for the ad-hoc analyses.

Results

Of 707 randomized patients (n = 352, PF-05280014; n = 355, trastuzumab-EU), 252 (71.6%) in the PF-05280014 and 251 (70.7%) in the trastuzumab-EU group discontinued treatment due to objective progression. Overall, 451 (63.8%) patients completed the study. Between groups (PF-05280014; trastuzumab-EU), estimated median TTDs were 12.25 and 12.06 months (p = 0.692); 61 (17.3%) and 67 (18.9%) patients died; stratified hazard ratio for OS was 0.929 (95% confidence interval 0.656–1.316; p = 0.339); estimated survival rates were 82.3 and 77.4% at 2 years and 77.2 and 75.3% at 3 years. The incidences of treatment-emergent adverse events (TEAEs) overall (98.6%; 96.6%) and for grades ≥3 (41.0%; 43.1%) were comparable between groups. In patients (n = 265; n = 264) ongoing after day 378, the incidences of any TEAEs, grade ≥3 TEAEs, and serious TEAEs were comparable between the treatment groups.

Conclusion

Long-term safety and OS were consistent with previous results and demonstrated no clinically meaningful differences between treatment groups.

Trial registration

ClinicalTrials.gov: NCT01989676 (21 November 2013); and EudraCT: 2013-001352-34 (18 December 2013).

中文翻译：

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PF-05280014（一种曲妥珠单抗生物类似药）治疗 HER2 阳性转移性乳腺癌患者的长期安全性和有效性：一项随机、双盲研究的最新结果

背景

在一项 III 期研究中，将 PF-05280014 与来自欧盟的曲妥珠单抗（曲妥珠单抗-EU）进行了比较，两者均加紫杉醇，作为人类表皮生长因子受体 2 阳性转移性乳腺癌的一线治疗。证明了治疗组之间的等效性。

客观的

本研究的目的是报告首例患者筛查后 6 年的长期安全性和总生存期 (OS)。

患者和方法

随机患者接受静脉注射 PF-05280014 或曲妥珠单抗-EU，每个都加紫杉醇，直到客观疾病进展。OS、长期安全性、亚组安全性（第 378 天后继续治疗的患者）和停药时间 (TTD) 根据针对临时分析修改的最终统计分析计划进行了评估。

结果

在 707 名随机患者（n  = 352，PF-05280014；n  = 355，曲妥珠单抗-EU）中，PF-05280014 中的 252 名（71.6%）和曲妥珠单抗-EU 组中的 251 名（70.7%）由于客观进展而停止治疗. 总体而言，451 名 (63.8%) 患者完成了研究。组间（PF-05280014；曲妥珠单抗-EU），估计的中位 TTD 分别为 12.25 和 12.06 个月（p  = 0.692）；61名（17.3%）和67名（18.9%）患者死亡；OS 的分层风险比为 0.929（95% 置信区间 0.656–1.316；p = 0.339); 估计 2 年生存率为 82.3% 和 77.4%，3 年生存率为 77.2% 和 75.3%。治疗中出现的不良事件 (TEAE) 总体 (98.6%; 96.6%) 和≥3 级 (41.0%; 43.1%) 的发生率在各组之间具有可比性。 在第 378 天后继续进行的患者（n  = 265；n = 264）中，任何 TEAE、≥3 级 TEAE 和严重 TEAE 的发生率在治疗组之间具有可比性。

结论

长期安全性和 OS 与之前的结果一致，并且治疗组之间没有临床意义的差异。

试用注册

ClinicalTrials.gov：NCT01989676（2013 年 11 月 21 日）；EudraCT：2013-001352-34（2013 年 12 月 18 日）。