曲妥珠单抗联合辅助化疗用于可手术的HER2阳性乳腺癌

Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer.

作者信息

Romond Edward H, Perez Edith A, Bryant John, Suman Vera J, Geyer Charles E, Davidson Nancy E, Tan-Chiu Elizabeth, Martino Silvana, Paik Soonmyung, Kaufman Peter A, Swain Sandra M, Pisansky Thomas M, Fehrenbacher Louis, Kutteh Leila A, Vogel Victor G, Visscher Daniel W, Yothers Greg, Jenkins Robert B, Brown Ann M, Dakhil Shaker R, Mamounas Eleftherios P, Lingle Wilma L, Klein Pamela M, Ingle James N, Wolmark Norman

机构信息

National Surgical Adjuvant Breast and Bowel Project, Pittsburgh, USA.

出版信息

N Engl J Med. 2005 Oct 20;353(16):1673-84. doi: 10.1056/NEJMoa052122.

DOI:10.1056/NEJMoa052122

PMID:16236738

Abstract

BACKGROUND

We present the combined results of two trials that compared adjuvant chemotherapy with or without concurrent trastuzumab in women with surgically removed HER2-positive breast cancer.

METHODS

The National Surgical Adjuvant Breast and Bowel Project trial B-31 compared doxorubicin and cyclophosphamide followed by paclitaxel every 3 weeks (group 1) with the same regimen plus 52 weeks of trastuzumab beginning with the first dose of paclitaxel (group 2). The North Central Cancer Treatment Group trial N9831 compared three regimens: doxorubicin and cyclophosphamide followed by weekly paclitaxel (group A), the same regimen followed by 52 weeks of trastuzumab after paclitaxel (group B), and the same regimen plus 52 weeks of trastuzumab initiated concomitantly with paclitaxel (group C). The studies were amended to include a joint analysis comparing groups 1 and A (the control group) with groups 2 and C (the trastuzumab group). Group B was excluded because trastuzumab was not given concurrently with paclitaxel.

RESULTS

By March 15, 2005, 394 events (recurrent, second primary cancer, or death before recurrence) had been reported, triggering the first scheduled interim analysis. Of these, 133 were in the trastuzumab group and 261 in the control group (hazard ratio, 0.48; P<0.0001). This result crossed the early stopping boundary. The absolute difference in disease-free survival between the trastuzumab group and the control group was 12 percent at three years. Trastuzumab therapy was associated with a 33 percent reduction in the risk of death (P=0.015). The three-year cumulative incidence of class III or IV congestive heart failure or death from cardiac causes in the trastuzumab group was 4.1 percent in trial B-31 and 2.9 percent in trial N9831.

CONCLUSIONS

Trastuzumab combined with paclitaxel after doxorubicin and cyclophosphamide improves outcomes among women with surgically removed HER2-positive breast cancer. (ClinicalTrials.gov numbers, NCT00004067 and NCT00005970.)

摘要

背景

我们展示了两项试验的联合结果，这两项试验比较了手术切除的HER2阳性乳腺癌女性患者接受辅助化疗时加用或不加用曲妥珠单抗的情况。

方法

国家外科辅助乳腺和肠道项目试验B-31比较了每3周给予阿霉素和环磷酰胺，随后给予紫杉醇的方案（第1组）与相同方案加从第一剂紫杉醇开始的52周曲妥珠单抗的方案（第2组）。北中部癌症治疗组试验N9831比较了三种方案：阿霉素和环磷酰胺，随后每周给予紫杉醇（A组）；相同方案，在紫杉醇后给予52周曲妥珠单抗（B组）；相同方案加与紫杉醇同时开始的52周曲妥珠单抗（C组）。研究进行了修正，纳入了一项联合分析，比较第1组和A组（对照组）与第2组和C组（曲妥珠单抗组）。B组被排除，因为曲妥珠单抗未与紫杉醇同时给予。

结果

到2005年3月15日，已报告394例事件（复发、第二原发性癌症或复发前死亡），触发了首次预定的中期分析。其中，133例在曲妥珠单抗组，261例在对照组（风险比，0.48；P<0.0001）。这一结果越过了早期停止界限。曲妥珠单抗组和对照组之间无病生存率的绝对差异在三年时为12%。曲妥珠单抗治疗使死亡风险降低了33%（P=0.015）。在试验B-31中，曲妥珠单抗组III级或IV级充血性心力衰竭或心脏原因死亡的三年累积发生率为4.1%，在试验N9831中为2.9%。