Octreotide LAR and tamoxifen versus tamoxifen in phase III randomize early breast cancer trials: NCIC CTG MA.14 and NSABP B-29.
Octreotide LAR and tamoxifen versus tamoxifen in phase III randomize early breast cancer trials: NCIC CTG MA.14 and NSABP B-29.
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奥曲肽 LAR 和他莫昔芬与他莫昔芬的 III 期随机早期乳腺癌试验：NCIC CTG MA.14 和 NSABP B-29。
DOI：
10.1007/s10549-015-3547-4
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发表时间：
2015
影响因子：
3.8
通讯作者：
Pollak,MichaelN
中科院分区：
文献类型：
--
作者：
Chapman,Judith-AnneW;Costantino,JosephP;Dong,Bin;Margolese,RichardG;Pritchard,KathleenI;Shepherd,LoisE;Gelmon,KarenA;Wolmark,Norman;Pollak,MichaelN
NCIC CTG MA.14和NSABP B-29试验检查了奥曲肽LAR （OCT）与5年他莫昔芬（TAM）的添加情况。胆囊毒性导致B-29停止OCT治疗，MA.14 OCT治疗缩短至2年。667 MA.14患者的中位随访时间为9.8年，893 B-29患者的中位随访时间为6.8年。主要终点是无病生存期（DFS），定义为从随机化到乳腺癌复发的时间；除鳞状或基底细胞皮肤癌、宫颈原位癌或乳腺小叶原位癌以外的第二原发癌；或死亡。主要统计检验为单变量合并分层log-rank检验；多变量评价采用Cox回归。对于MA.14, 97%的患者年龄≥50岁；B-29为62%。MA.14为53%淋巴结阴性（LN−），B-29为100% LN−；MA.14患者中33%接受辅助化疗，2%同时接受化疗，而B-29患者中53%同时接受化疗。MA.14例90%激素受体阳性；B-29, 100%。14例患者的5年DFS为TAM组80%，TAM + OCT组76%；B-29患者双臂的5年DFS为88%。合并单变量TAM + OCT与TAM的风险比（HR）为0.99 (95% CI 0.81-1.20, p= 0.69)； MA.14的风险比（HR）为0.94 (0.73-1.20,p= 0.50)；对于B-29， HR = 1.09 （0.80-1.50;p= 0.59）。多变量合并HR = 0.98 （0.81-1.20;p= 0.84）。年龄较大（p< 0.001）、T分期较高（p< 0.001）和LN + (p< 0.001)患者的DFS较短。在TAM中加入OCT对DFS无显著改善；胆囊毒性缩短了oct的额外给药时间。这并不否定针对胰岛素- igf - 1受体家族的毒性较小的治疗方法。
NCIC CTG MA.14 and NSABP B-29 trials examined the addition of Octreotide LAR (OCT) to 5 years of tamoxifen (TAM). Gallbladder toxicity led to B-29 discontinuation of OCT, and MA.14 OCT administration shortened to 2 years. Median follow-up was 9.8 years for 667 MA.14 patients and 6.8 years for 893 B-29 patients. The primary endpoint was disease-free survival (DFS), defined as time from randomization to time of breast cancer recurrence; second primary cancer other than squamous or basal cell skin carcinoma, cervical carcinoma in situ, or lobular breast carcinoma in situ; or death. The primary statistical test was a univariable pooled stratified log-rank test; multivariable assessment was with Cox regression. For MA.14, 97 % of patients were ≥50 years; for B-29, 62 %. MA.14 patients were 53 % lymph node negative (LN−) while B-29 were 100 % LN−; 33 % of MA.14 patients received adjuvant chemotherapy, 2 % concurrently, while B-29 had 53 % concurrent chemotherapy. MA.14 patients were 90% hormone receptor positive; B-29, 100 %. MA.14 patients experienced 5-year DFS of 80 % with TAM, 76 % with TAM + OCT; B-29 patients had 5-year DFS of 88 % for both arms. Pooled univariable TAM + OCT to TAM hazard ratio (HR) was 0.99 (95% CI 0.81–1.20;p= 0.69): for MA.14, HR = 0.94 (0.73–1.20;p= 0.50); for B-29, HR = 1.09 (0.80–1.50;p= 0.59). Multivariable pooled HR = 0.98 (0.81–1.20;p= 0.84). Older patients (p< 0.001), with higher T stage (p< 0.001), and LN + (p< 0.001) had shorter DFS. Addition of OCT to TAM did not significantly improve DFS; gallbladder toxicity shortened the additional administration of OCT. This does not negate targeting the insulin–IGF-I receptor family with less toxic therapeutics.