芳香化酶抑制剂和失活剂与标准激素疗法治疗晚期乳腺癌的生存情况：荟萃分析

Survival with aromatase inhibitors and inactivators versus standard hormonal therapy in advanced breast cancer: meta-analysis.

作者信息

Mauri Davide, Pavlidis Nicholas, Polyzos Nikolaos P, Ioannidis John P A

机构信息

Department of Medical Oncology, University of Ioannina School of Medicine, Ioannina 45110, Greece.

出版信息

J Natl Cancer Inst. 2006 Sep 20;98(18):1285-91. doi: 10.1093/jnci/djj357.

DOI:10.1093/jnci/djj357

PMID:16985247

Abstract

BACKGROUND

Aromatase inhibitors and inactivators have been extensively tested in patients with advanced breast cancer, but it is unclear whether they offer any survival benefits compared with standard hormonal treatment with tamoxifen or progestagens. We performed a meta-analysis of randomized controlled trials that compared several generations of aromatase inhibitors and inactivators with standard hormonal treatment in patients with advanced breast cancer.

METHODS

The endpoint that we assessed was survival. Trials were located through searches of PubMed and Cochrane Library (last update March 2006). Relative hazards (RHs) were summarized across trials through fixed- and random-effects analyses, and heterogeneity was assessed with the Q and I2 statistics. All statistical tests were two-sided.

RESULTS

Twenty-five different comparisons, with a total of 8504 patients, were included in the meta-analysis. We found statistically significant survival benefits with third-generation aromatase inhibitors and inactivators (vorozole, letrozole, examestane, and anastrazole) (RH = 0.87, 95% confidence interval [CI] = 0.82 to 0.93; P<.001) but not with first-generation (aminoglutethimide) or second-generation (formestane and fadrozole) agents. The difference in the summary effects between these two groups of trials was statistically significant (P = .04). The survival benefit with third-generation agents in first-line trials, in which these agents were compared with tamoxifen (11% RH reduction, 95% CI = 1% to 19%; P = .03), was identical to their benefit in second- and subsequent-line trials in which these agents were compared with other treatments (14% RH reduction, 95% CI = 6% to 21%; P<.001).

CONCLUSIONS

Inhibition of the aromatase system, in particular with third-generation aromatase inhibitors and inactivators, appears to be associated with statistically significant improved survival of patients with advanced breast cancer compared with standard hormonal treatments.

摘要

背景

芳香化酶抑制剂和灭活剂已在晚期乳腺癌患者中进行了广泛测试，但与他莫昔芬或孕激素的标准激素治疗相比，它们是否能带来生存益处尚不清楚。我们对随机对照试验进行了荟萃分析，比较了几代芳香化酶抑制剂和灭活剂与晚期乳腺癌患者的标准激素治疗。

方法

我们评估的终点是生存。通过检索PubMed和Cochrane图书馆（最后更新时间为2006年3月）来查找试验。通过固定效应和随机效应分析汇总各试验的相对风险（RHs），并使用Q和I²统计量评估异质性。所有统计检验均为双侧检验。

结果

荟萃分析纳入了25种不同的比较，共8504例患者。我们发现第三代芳香化酶抑制剂和灭活剂（伏罗唑、来曲唑、依西美坦和阿那曲唑）具有统计学显著的生存益处（RH = 0.87，95%置信区间[CI] = 0.82至0.93；P <.001），而第一代（氨鲁米特）或第二代（福美坦和法倔唑）药物则没有。这两组试验的汇总效应差异具有统计学意义（P =.04）。第三代药物在一线试验中的生存益处，即与他莫昔芬相比（RH降低11%，95% CI = 1%至19%；P =.03），与在二线及后续试验中的益处相同，即在这些试验中与其他治疗方法相比（RH降低14%，95% CI = 6%至21%；P <.001）。