Ganesan Prasanth, Moulder Stacy, Lee J Jack, Janku Filip, Valero Vicente, Zinner Ralph G, Naing Aung, Fu Siqing, Tsimberidou Apostolia M, Hong David, Stephen Bettzy, Stephens Philip, Yelensky Roman, Meric-Bernstam Funda, Kurzrock Razelle, Wheler Jennifer J
Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program), The University of Texas MD Anderson Cancer Center, Houston, Texas.
Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Mol Cancer Ther. 2014 Dec;13(12):3175-84. doi: 10.1158/1535-7163.MCT-14-0358. Epub 2014 Sep 24.
Patients with metastatic triple-negative breast cancer (TNBC) have poor treatment outcomes. We reviewed the electronic records of consecutive patients with metastatic TNBC treated in phase I clinic at MD Anderson Cancer Center (Houston, TX) between Augu st 2005 and May 2012. One hundred and six patients received at least 1 phase I trial. Twelve of 98 evaluable patients (12%) had either complete response (CR; n = 1), partial response (PR; n = 7), or stable disease ≥ 6 months (SD; n = 4). Patients treated on matched therapy (n = 16) compared with those on nonmatched therapy (n = 90) had improved SD ≥ 6 months/PR/CR (33% vs. 8%; P = 0.018) and longer progression-free survival (PFS; median, 6.4 vs. 1.9 months; P = 0.001). Eleven of 57 evaluable patients (19%) treated with combination chemotherapy and targeted therapy had SD ≥ 6 months/PR/CR versus 1 of 41 evaluable patients (2%) treated on other phase I trials (P = 0.013), and longer PFS (3.0 vs. 1.6 months; P < 0.0001). Patients with molecular alterations in the PI3K/AKT/mTOR pathway treated on matched therapy (n = 16) had improved PFS compared with those with and without molecular alterations treated on nonmatched therapy (n = 27; 6.4 vs. 3.2 months; P = 0.036). On multivariate analysis, improved PFS was associated with treatment with combined chemotherapy and targeted agents (P = 0.0002), ≤ 2 metastatic sites (P = 0.003), therapy with PI3K/AKT/mTOR inhibitors for those with cognate pathway abnormalities (P = 0.018), and treatment with antiangiogenic agents (P = 0.023). In summary, combinations of chemotherapy and angiogenesis and/or PI3K/AKT/mTOR inhibitors demonstrated improved outcomes in patients with metastatic TNBC.
转移性三阴性乳腺癌（TNBC）患者的治疗效果较差。我们回顾了2005年8月至2012年5月期间在德克萨斯州休斯顿市MD安德森癌症中心I期临床治疗的连续性转移性TNBC患者的电子病历。106例患者接受了至少1次I期试验。98例可评估患者中有12例（12%）获得完全缓解（CR；n = 1）、部分缓解（PR；n = 7）或疾病稳定≥6个月（SD；n = 4）。接受匹配治疗的患者（n = 16）与接受非匹配治疗的患者（n = 90）相比，疾病稳定≥6个月/部分缓解/完全缓解的比例有所提高（33%对8%；P = 0.018），无进展生存期更长（PFS；中位数，6.4个月对1.9个月；P = 0.001）。57例接受联合化疗和靶向治疗的可评估患者中有11例（19%）疾病稳定≥6个月/部分缓解/完全缓解，而在其他I期试验中接受治疗的41例可评估患者中有1例（2%）达到此效果（P = 0.013），且无进展生存期更长（3.0个月对1.6个月；P < 0.0001）。接受匹配治疗的PI3K/AKT/mTOR通路存在分子改变的患者（n = 16）与接受非匹配治疗的有和无分子改变的患者（n = 27）相比，无进展生存期有所改善（6.4个月对3.2个月；P = 0.036）。多因素分析显示，无进展生存期的改善与联合化疗和靶向药物治疗（P = 0.0002）、转移部位≤2个（P = 0.003）、针对同源通路异常患者使用PI3K/AKT/mTOR抑制剂治疗（P = 0.018）以及使用抗血管生成药物治疗（P = 0.023）相关。总之，化疗与血管生成抑制剂和/或PI3K/AKT/mTOR抑制剂联合使用可改善转移性TNBC患者的治疗效果。
