Medical Lead Department, Translational Research in Oncology (TRIO), Montevideo, Uruguay.
Biostatistics, Translational Research in Oncology (TRIO), Edmonton.
Ann Oncol. 2017 Aug 1;28(8):1836-1841. doi: 10.1093/annonc/mdx264.
Recent retrospective studies suggest that beta-adrenergic blocking drugs (BB) are associated with improved outcomes in patients with a range of cancers. Although limited and discordant data suggest that BB may increase overall survival (OS) in localized breast cancer (BC), there is no information on the effects of BB in women with advanced BC.
To explore the association between BB use and BC outcomes, we retrospectively reviewed ROSE/TRIO-012, a double-blinded, multinational phase III trial that randomized 1144 patients with HER2-negative advanced BC to first-line docetaxel in combination with ramucirumab or placebo. We compared progression-free survival (PFS), OS, overall response rate, and clinical benefit rate in patients who received BB to those who did not.
153/1144 (13%) patients received BB; 62% prior to enrolment and 38% began after enrolment. Median PFS in BB treated patients was longer than in patients who did not receive them (10.3 versus 8.3 months; HR 0.81; 95% CI 0.66-0.99; P = 0.038). Patients treated with BB only after enrolment had even higher median PFS (15.5 versus 8.3 months, P < 0.001). In the TNBC subset, median PFS was 13.0 months with BB, compared to 5.2 months without BB (HR 0.52; 95% CI 0.34-0.79; P = 0.002). The benefit of BB intake in PFS was independent of treatment-emergent hypertension (P = 0.476) but associated with treatment arm (P = 0.037). The test for interactions between BB and treatment arm was not significant (P = 0.276). No differences were seen in OS, overall response rate, or clinical benefit rate. A validation dataset analysis had consistent but less substantial improved outcomes for women with node positive operable breast cancer receiving BB in the BCIRG-005 trial.
In this exploratory analysis, BB intake was associated with significant improvement in PFS, particularly in patients with TNBC and patients not previously exposed to BB.
NCT00703326.
最近的回顾性研究表明，β-肾上腺素能阻滞剂（BB）可改善多种癌症患者的预后。尽管有限且不一致的数据表明 BB 可能会增加局部乳腺癌（BC）的总生存期（OS），但尚无关于 BB 在晚期 BC 女性中作用的信息。
为了探讨 BB 使用与 BC 结局之间的关联，我们回顾性分析了 ROSE/TRIO-012，这是一项双盲、多中心的 III 期试验，该试验将 1144 例 HER2 阴性晚期 BC 患者随机分配至一线多西紫杉醇联合雷莫芦单抗或安慰剂治疗。我们比较了接受 BB 和未接受 BB 的患者的无进展生存期（PFS）、OS、总缓解率和临床获益率。
1144 例患者中有 153 例（13%）接受了 BB；62%在入组前，38%在入组后开始使用。接受 BB 治疗的患者中位 PFS 长于未接受 BB 治疗的患者（10.3 个月 vs 8.3 个月；HR 0.81；95%CI 0.66-0.99；P=0.038）。仅在入组后接受 BB 治疗的患者中位 PFS 更高（15.5 个月 vs 8.3 个月，P<0.001）。在三阴性乳腺癌（TNBC）亚组中，接受 BB 治疗的患者中位 PFS 为 13.0 个月，而未接受 BB 治疗的患者为 5.2 个月（HR 0.52；95%CI 0.34-0.79；P=0.002）。BB 摄入对 PFS 的获益与治疗后高血压无关（P=0.476），但与治疗臂有关（P=0.037）。BB 与治疗臂之间交互作用的检验无统计学意义（P=0.276）。OS、总缓解率或临床获益率无差异。在 BCIRG-005 试验中，对接受 BB 的淋巴结阳性可手术乳腺癌女性的验证数据集分析显示，OS 有更显著的改善。
在这项探索性分析中，BB 摄入与 PFS 的显著改善相关，尤其是在 TNBC 患者和以前未接受过 BB 治疗的患者中。
NCT00703326。
