Multicentric neoadjuvant phase II study of panitumumab combined with an anthracycline/taxane-based chemotherapy in operable triple-negative breast cancer: identification of biologically defined signatures predicting treatment impact
Multicentric neoadjuvant phase II study of panitumumab combined with an anthracycline/taxane-based chemotherapy in operable triple-negative breast cancer: identification of biologically defined signatures predicting treatment impact
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DOI：
10.1093/annonc/mdu183
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发表时间：
2014-08-01
影响因子：
50.5
通讯作者：
Penault-Llorca, F.
中科院分区：
文献类型：
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作者：
Nabholtz, J. M.;Abrial, C.;Penault-Llorca, F.
背景资料：三阴性乳腺癌（TNBC）是一组异质性肿瘤，其中一些上皮生长因子受体（EGFR）途径可能发挥重要作用。我们研究了抗EGFR抗体（帕尼单抗）与标准的新辅助蒽环类紫杉烷为基础的化疗在可手术的患者的疗效和毒性，阶段II-III，TNBC.Patients和方法：治疗在这个多中心的新辅助试验研究包括帕尼单抗（9毫克/公斤）八个周期q。3周联合4个周期的5-氟尿嘧啶、表阿霉素和环磷酰胺（FEC 100：500/100/500 mg/m2）q.多西他赛（T：100 mg/m2）q. 3周治疗后，所有患者均接受手术切除。可评估患者的病理完全缓解（pCR）是主要终点，而临床反应、毒性和辅助研究是次要终点。石蜡包埋和冷冻的肿瘤样本进行了系统的收集，目的是确定预测生物标志物的疗效和耐药性，以选择生物学定义的亚群潜在的进一步临床开发的抗EGFR antibody.Results：60例患者包括47评估病理反应。根据Chevallier和Sataloff分类，pCR率分别为46.8% [95%置信区间（CI）：32.5%-61.1%]和55.3% [95% CI：41.1%-69.5%]。完全临床缓解率（cCR）为37.5%。87%的病例进行了保守手术。毒性是可控的。一方面，高EGFR和低细胞角蛋白8/18在肿瘤细胞中的表达，另一方面，高密度的CD 8+肿瘤浸润淋巴细胞的关联显着预测pCR.Conclusions：帕尼单抗与FEC 100，其次是多西他赛组合出现有效的，与可接受的毒性，作为新辅助治疗的可操作的TNBC。几种生物标志物可以帮助定义具有高概率pCR的患者的大子集，这表明在生物学定义的TNBC患者亚组中进一步开发这种组合的潜在兴趣。
Background: Triple-negative breast cancer (TNBC) is a heterogeneous group of tumors for some of which the epithelial growth factor receptor (EGFR) pathway may play an important role. We investigated the efficacy and toxicity of an anti-EGFR antibody (panitumumab) combined with a standard neoadjuvant anthracycline-taxane-based chemotherapy in patients with operable, stage II-III, TNBC.Patients and methods: Treatment in this multicentric neoadjuvant pilot study consisted of panitumumab (9 mg/kg) for eight cycles q. 3 weeks combined with four cycles of 5-fluorouracil, epidoxorubicin and cyclophosphamide (FEC100: 500/100/500 mg/m(2)) q. 3 weeks, followed by four cycles of docetaxel (T: 100 mg/m2) q. 3 weeks. Following therapy, all patients underwent surgical resection. Pathologic complete response (pCR) in assessable patients was the main end point while clinical response, toxicity and ancillary studies were secondary end points. Paraffin-embedded and frozen tumor samples were systematically collected with the aim to identify predictive biomarkers of efficacy and resistance in order to select biologically defined subpopulations for potential further clinical development of the anti-EGFR antibody.Results: Sixty patients were included with 47 assessable for pathologic response. The pCR rates were 46.8% [95% confidence interval (CI): 32.5% to 61.1%] and 55.3% [95% CI: 41.1% to 69.5%] according, respectively, to Chevallier and Sataloff classifications. The complete clinical response (cCR) rate was 37.5%. Conservative surgery was carried out in 87% of cases. Toxicity was manageable. The association of high EGFR and low cytokeratin 8/18 expression in tumor cells on one hand and high density of CD8+ tumor-infiltrating lymphocytes on the other hand were significantly predictive of pCR.Conclusions: Panitumumab in combination with FEC100 followed by docetaxel appears efficacious, with acceptable toxicity, as neoadjuvant therapy of operable TNBC. Several biomarkers could help define large subsets of patients with a high probability of pCR, suggesting a potential interest to further develop this combination in biologically defined subgroups of patients with TNBC.