Clinical Effectiveness Unit, The Royal College of Surgeons of England, London, UK; Department of Health Services Research & Policy, London School of Hygiene & Tropical Medicine, London, UK.
Nuffield Department of Population Health, University of Oxford, Oxford, UK.
Eur J Cancer. 2024 Nov;211:114309. doi: 10.1016/j.ejca.2024.114309. Epub 2024 Sep 14.
Randomised controlled trials (RCTs) reported adjuvant trastuzumab-based treatment improved overall survival (OS) among patients with HER2-positive early invasive breast cancer (EIBC). Few RCTs included older patients or those with comorbidity/frailty. This study aimed to determine whether the effect of adjuvant trastuzumab-based treatment on survival outcomes varies by patient age and fitness, using national data from routine care.
Women (50+ years) newly-diagnosed with HER2-positive EIBC between 2014 and 2019 were identified from England Cancer Registry data. Registration records were linked to Systemic Anti-Cancer Therapy data for treatment details and ONS death register for mortality details. A propensity score analysis employing the inverse probability of treatment weighting method was used to balance the patient variables across treatment groups. Cox models were used to evaluate whether the effect of treatment on OS was associated with patient age and fitness; competing risks regression models were used for breast cancer-specific survival (BCSS).
5238 women initiated adjuvant trastuzumab-based treatment. Median follow-up was 56.7 months. Comparison with 3421 women who did not receive adjuvant trastuzumab highlighted differences at diagnosis in relation to age, fitness, grade, nodal involvement, surgery type and use of radiotherapy. Weighted survival analysis found trastuzumab was associated with improved OS (hazard ratio HR 0.56, 95 %CI: 0.45-0.70) and improved BCSS (subHR 0.62, 95 %CI: 0.47-0.82). We found no evidence of a difference in effect by age or patient fitness for either outcome.
In this national dataset, adjuvant trastuzumab was associated with improvements in survival, with an OS effect size similar to RCT evidence. The effect size was not found to vary by patient age or fitness. Chronological age and fitness alone should not be barriers to receipt of effective adjuvant targeted treatment.
随机对照试验(RCT)报告称,曲妥珠单抗辅助治疗可改善 HER2 阳性早期浸润性乳腺癌(EIBC)患者的总生存期(OS)。很少有 RCT 纳入老年患者或合并症/虚弱患者。本研究旨在使用常规护理中的全国性数据,确定曲妥珠单抗辅助治疗对生存结果的影响是否因患者年龄和健康状况而异。
从英格兰癌症登记处的数据中确定了 2014 年至 2019 年间新诊断为 HER2 阳性 EIBC 的 50 岁及以上女性。登记记录与系统抗癌治疗数据相关联,以获取治疗细节,与 ONS 死亡登记处相关联,以获取死亡率细节。采用逆概率治疗加权法的倾向评分分析用于平衡治疗组之间的患者变量。Cox 模型用于评估治疗对 OS 的影响是否与患者年龄和健康状况相关;竞争风险回归模型用于乳腺癌特异性生存(BCSS)。
5238 名女性开始接受曲妥珠单抗辅助治疗。中位随访时间为 56.7 个月。与 3421 名未接受曲妥珠单抗辅助治疗的女性相比,在诊断时,年龄、健康状况、分级、淋巴结受累、手术类型和放疗使用方面存在差异。加权生存分析发现,曲妥珠单抗与 OS 改善相关(风险比 HR 0.56,95%CI:0.45-0.70)和 BCSS 改善(亚 HR 0.62,95%CI:0.47-0.82)。我们没有发现这两种结局的效果在年龄或患者健康状况方面存在差异的证据。
在这个全国性数据集中,曲妥珠单抗辅助治疗与生存改善相关,OS 的效果大小与 RCT 证据相似。未发现治疗效果因患者年龄或健康状况而异。单纯的年龄和健康状况不应成为接受有效辅助靶向治疗的障碍。