Department of Surgical Oncology, Orlando Health Cancer Institute, Orlando, FL, USA.
NRG Oncology SDMC, and the Department of Biostatistics, University of Pittsburgh, Pittsburgh, PA, USA.
J Natl Cancer Inst. 2023 Nov 8;115(11):1302-1309. doi: 10.1093/jnci/djad078.
The National Surgical Adjuvant Breast and Bowel Project B-42 trial evaluated extended letrozole therapy (ELT) in postmenopausal breast cancer patients who were disease free after 5 years of aromatase inhibitor (AI)-based therapy. Seven-year results demonstrated a nonstatistically significant trend in disease-free survival (DFS) in favor of ELT. We present 10-year outcome results.
In this double-blind, phase III trial, patients with stage I-IIIA hormone receptor-positive breast cancer, disease free after 5 years of an AI or tamoxifen followed by an AI, were randomly assigned to 5 years of letrozole or placebo. Primary endpoint was DFS, defined as time from random assignment to breast cancer recurrence, second primary malignancy, or death. All statistical tests are 2-sided.
Between September 2006 and January 2010, 3966 patients were randomly assigned (letrozole: 1983; placebo: 1983). Median follow-up time for 3923 patients included in efficacy analyses was 10.3 years. There was statistically significant improvement in DFS in favor of letrozole compared with placebo (hazard ratio [HR] = 0.85, 95% confidence interval [CI] = 0.74 to 0.96; P = .01; 10-year DFS: placebo = 72.6%, letrozole = 75.9%, absolute difference = 3.3%). There was no difference in the effect of letrozole on overall survival (HR = 0.97, 95% CI = 0.82 to 1.15; P = .74). Letrozole statistically significantly reduced breast cancer-free interval events (HR = 0.75, 95% CI = 0.62 to 0.91; P = .003; absolute difference in cumulative incidence = 2.7%) and distant recurrences (HR = 0.72, 95% CI = 0.55 to 0.92; P = .01; absolute difference = 1.8%). The rates of osteoporotic fractures and arterial thrombotic events did not differ between treatment groups.
The beneficial effect of ELT on DFS persisted at 10 years. Letrozole also improved breast cancer-free interval and distant recurrences without improving overall survival. Careful assessment of potential risks and benefits is necessary for selecting appropriate candidates for ELT.
国家外科辅助乳腺和肠道项目 B-42 试验评估了延长来曲唑治疗（ELT）在接受芳香酶抑制剂（AI）治疗 5 年后无疾病的绝经后乳腺癌患者中的效果。7 年的结果显示 ELT 在无病生存期（DFS）方面具有非统计学意义的优势趋势。我们目前报告的是 10 年的结果。
在这项双盲、三期临床试验中，患有激素受体阳性乳腺癌的 I 期-IIIA 期患者，在 AI 或他莫昔芬治疗 5 年后无疾病，随机分配接受 5 年的来曲唑或安慰剂治疗。主要终点是 DFS，定义为从随机分组到乳腺癌复发、第二原发恶性肿瘤或死亡的时间。所有统计检验均为双侧检验。
2006 年 9 月至 2010 年 1 月，3966 例患者被随机分配（来曲唑组：1983 例；安慰剂组：1983 例）。3923 例可进行疗效分析的患者的中位随访时间为 10.3 年。与安慰剂相比，来曲唑组的 DFS 显著改善，有利于来曲唑（风险比[HR] = 0.85，95%置信区间[CI] = 0.74 至 0.96；P =.01；10 年 DFS：安慰剂组=72.6%，来曲唑组=75.9%，绝对差异=3.3%）。来曲唑对总生存的影响没有差异（HR = 0.97，95%CI = 0.82 至 1.15；P =.74）。来曲唑统计学上显著降低了无乳腺癌间期事件（HR = 0.75，95%CI = 0.62 至 0.91；P =.003；累积发生率的绝对差异=2.7%）和远处复发（HR = 0.72，95%CI = 0.55 至 0.92；P =.01；绝对差异=1.8%）。治疗组的骨质疏松性骨折和动脉血栓栓塞事件发生率没有差异。
ELT 对 DFS 的有益影响在 10 年后仍然存在。来曲唑还改善了无乳腺癌间期和远处复发，而没有改善总生存。在选择合适的 ELT 候选者时，需要仔细评估潜在的风险和获益。
