Cinieri Saverio, Chan Arlene, Altundag Kadri, Vandebroek An, Tubiana-Mathieu Nicole, Barnadas Agusti, Dodyk Patricia, Lazzarelli Silvia, Botha Michiel, Rauch Daniel, Villanova Gustavo, Coskun Ugur
Medical Oncology and Breast Unit, European Institute of Oncology (IRCCS), Milan, and San Antonio Perrino Hospital, Brindisi, Italy.
Breast Cancer Research Centre-WA and Curtin University, Perth, Australia.
Clin Breast Cancer. 2017 Apr;17(2):91-99.e1. doi: 10.1016/j.clbc.2016.06.014. Epub 2016 Jun 25.
The purpose of this study was to evaluate the efficacy of 3 first-line chemotherapy combination regimens for HER2-negative metastatic breast cancer (mBC).
In this open-label, 3-arm, randomized phase II trial, patients were randomized to all-oral NORCAP (vinorelbine/capecitabine), GEMPAC (gemcitabine/paclitaxel), or GEMDOC (gemcitabine/docetaxel) as first-line chemotherapy for HER2-negative mBC. Stratification factors were center, previous (neo)adjuvant anthracycline, and age. The primary end point was disease control rate (DCR; complete or partial response, or stable disease for ≥3 months).
The DCR was 73% (95% confidence interval [CI], 59-85) with NORCAP (36 of 49 patients), 78% (95% CI, 64-88) with GEMPAC (39 of 50 patients), and 80% (95% CI, 66-90) with GEMDOC (40 of 50 patients). Objective response rates were 33% (16 of 49 patients), 24% (12 of 50 patients), and 50% (25 of 50 patients), respectively; median progression-free survival was 7.6, 9.0, and 11.4 months, respectively. Median overall survival was 30 to 31 months with all regimens. The most common Grade ≥3 adverse event with each regimen was neutropenia (24 patients [50%], 23 patients [46%], and 43 patients [86%], respectively). The most common nonhematological Grade ≥3 adverse event was fatigue. Grade 2 alopecia occurred in 36 patients (72%) who received GEMPAC and 38 patients (76%) who received GEMDOC, but only 4 patients (8%) who received NORCAP. There was no evidence of a detrimental effect of NORCAP on quality of life.
All-oral NORCAP is an active first-line chemotherapy regimen and might be offered as an alternative to first-line taxane-based therapy for HER2-negative mBC, particularly if patients wish to avoid alopecia or frequent intravenous administrations.
本研究旨在评估三种一线化疗联合方案对人表皮生长因子受体2(HER2)阴性转移性乳腺癌(mBC)的疗效。
在这项开放标签、三臂、随机II期试验中,患者被随机分配接受全口服NORCAP(长春瑞滨/卡培他滨)、GEMPAC(吉西他滨/紫杉醇)或GEMDOC(吉西他滨/多西他赛)作为HER2阴性mBC的一线化疗。分层因素为中心、既往(新)辅助蒽环类药物使用情况和年龄。主要终点为疾病控制率(DCR;完全缓解或部分缓解,或疾病稳定≥3个月)。
NORCAP组的DCR为73%(95%置信区间[CI],59 - 85)(49例患者中的36例),GEMPAC组为78%(95%CI,64 - 88)(50例患者中的39例),GEMDOC组为80%(95%CI,66 - 90)(50例患者中的40例)。客观缓解率分别为33%(49例患者中的16例)、24%(50例患者中的12例)和50%(50例患者中的25例);无进展生存期的中位数分别为7.6、9.0和11.4个月。所有方案的总生存期中位数为30至31个月。每种方案最常见的≥3级不良事件是中性粒细胞减少(分别为24例患者[50%]、23例患者[46%]和43例患者[86%])。最常见的非血液学≥3级不良事件是疲劳。接受GEMPAC的36例患者(72%)和接受GEMDOC的38例患者(76%)出现2级脱发,但接受NORCAP的患者中只有4例(8%)出现。没有证据表明NORCAP对生活质量有不利影响。
全口服NORCAP是一种有效的一线化疗方案,可作为HER2阴性mBC一线紫杉类药物治疗的替代方案,特别是当患者希望避免脱发或频繁静脉给药时。