Background: Trastuzumab is a key component of therapy for human epidermal growth receptor 2 (HER2) positive breast cancer. Because real-world data are lacking, the present research was conducted to evaluate the actual use of and the effectiveness of trastuzumab in the real world in China.
Methods: Inpatients with HER2 positive invasive breast cancer from 13 hospitals in Eastern China (2010-2015, n = 1,139) were included in this study. We aimed to assess the actual use of trastuzumab and to evaluate potential efficacy from trastuzumab in real-world research.
Results: Of 1,017 patients with early stage breast cancer (EBC), 40.5% (412/1,017) received trastuzumab therapy. Patients with EBC in resource-abundant regions (gross domestic product per capita >$15,000 and trastuzumab included in Medicare) are more likely to receive trastuzumab than those in resource-limited regions (37.3% vs. 13.0%, p < .05). After metastasis, 50.8% (366/720) patients received trastuzumab as their first-line therapy. More than 10% of patients with metastatic breast cancer (MBC) continued trastuzumab therapy after twice progression in resource-abundant regions, whereas more than 40% of patients never received any trastuzumab therapy during the whole course of therapy in resource-limited regions. Overall, the improvement in survival for trastuzumab versus non-trastuzumab was substantial in EBC (hazard ratio [HR] = 0.609, 95% confidence interval [CI]: 0.505-0.744) and in MBC (HR = 0.541, 95% CI: 0.418-0.606). This association was greater for patients with MBC who had never received trastuzumab (HR = 0.493, 95% CI: 0.372-0.576) than for those who had received adequate trastuzumab therapy in EBC stage (HR = 0.878, 95% CI: 0.506-1.431).
Conclusion: This study showed great disparities in trastuzumab use in different regions and different treatment stages. Both EBC and MBC patients can benefit from trastuzumab, as the survival data show; however, when trastuzumab is adequate in the early stage, a further trastuzumab-based therapy in first-line treatment of MBC will be ineffective, especially for those with short disease-free survival, and a second line of anti-HER2 therapy will be recommended. (Research number: CSCO-BC RWS 15001).
Implications for practice: This article explores the disparities in the rates of trastuzumab use due to the inequitable allocation of medical resources in China. The irrational use can be found both in resource-abundant regions and in resource-limited regions. Although trastuzumab-based therapy improved survival, the actual use of trastuzumab in the early stage of breast cancer may influence the subsequent therapeutic effect after metastasis. These findings from real-world research could help to optimize HER2 therapy after metastasis, especially in regions with limited access to these expensive targeted drugs.
摘要
背景.曲妥珠单抗是用于人类表皮生长因子受体2（HER2）阳性乳腺癌治疗的重要组成部分。由于缺少真实世界数据, 本研究旨在评价曲妥珠单抗在中国真实世界中的实际应用和疗效。
方法.本研究纳入了华东地区13个医院（2010‐2015年, n=1 139）的HER2阳性浸润性乳腺癌住院患者。我们旨在评估曲妥珠单抗在真实世界研究中的实际应用和潜在疗效。
结果.在1 017例早期乳腺癌患者（EBC）中, 40.5％（412/1 017）接受了曲妥珠单抗治疗。资源丰富地区的EBC患者（人均国民生产总值>15 000美元, 曲妥珠单抗被纳入医保）比资源有限地区更有可能接受曲妥珠单抗治疗（37.3％ vs. 13.0％, p <0.05）。转移后, 50.8％（366/720）患者接受了作为一线治疗的曲妥珠单抗治疗。在资源丰富的地区, 两次进展后超过10％的转移性乳腺癌患者（MBC）继续接受曲妥珠单抗治疗, 而在资源有限的地区, 超过40％的患者在整个治疗过程中从未接受过任何曲妥珠单抗治疗。总体而言, 在EBC患者中, 与非曲妥珠单抗组相比, 曲妥珠单抗组患者的生存期显著改善[风险比（HR）=0.609, 95%置信区间（CI）：0.505‐0.744], 在MBC患者中, 与非曲妥珠单抗组相比, 曲妥珠单抗组患者的生存期显著改善（HR=0.541, 95%CI：0.418‐0.606）。从未接受过曲妥珠单抗治疗的MBC患者（HR=0.493, 95%CI：0.372‐0.576）的这种关联优于在EBC期接受了足够曲妥珠单抗治疗的患者（HR=0.878, 95%CI: 0.506–1.431）。
结论.本研究显示曲妥珠单抗在不同地区和不同治疗阶段使用的差异很大。生存期数据显示, EBC和MBC患者均可从曲妥珠单抗治疗中获益；然而, 当在早期接受了足够的曲妥珠单抗治疗时, 在MBC的一线治疗中进一步接受基于曲妥珠单抗的治疗将是无效的, 尤其是对于无病生存期较短的患者, 因此建议采用二线抗HER2治疗。（研究编号： CSCO‐BC RWS 15001）。
Keywords: Human epidermal growth receptor 2 positive breast cancer; Medical resource disparity; Real‐world research; Survival.
© AlphaMed Press 2017.