转移性乳腺癌患者循环肿瘤细胞敏感性谱预测顺铂化疗反应的前瞻性评估
Prospective Evaluation of a Circulating Tumor Cell Sensitivity Profile to Predict Response to Cisplatin Chemotherapy in Metastatic Breast Cancer Patients.
作者信息
de Kruijff I E, Sieuwerts A M, Beije N, Prager-van der Smissen W J C, Angus L, Beaufort C M, Van M N, Oomen-de Hoop E, Jager A, Hamberg P, de Jongh F E, Kraan J, Martens J W M, Sleijfer S
机构信息
Department of Medical Oncology & Cancer Genomics Netherlands, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, Netherlands.
Department of Medical Oncology, Franciscus Gasthuis & Vlietland, Rotterdam, Netherlands.
出版信息
Front Oncol. 2021 Jun 25;11:697572. doi: 10.3389/fonc.2021.697572. eCollection 2021.
BACKGROUND
Cisplatin (cDDP) has regained interest for metastatic breast cancer (MBC) patients, given the platinum sensitivity in subtypes and better manageable toxicity. Here, the primary aim was to determine whether molecular characteristics of circulating tumor cells (CTCs) could identify patients responding to cDDP and to describe the outcomes to cDDP monotherapy in a large group of MBC patients pretreated with anthracycline- and taxane-based treatments.
METHODS
Based on cell line data, a CTC-cDDP-sensitivity profile was generated. Applying an A'Herns single-stage phase II design, further investigation was considered worthwhile if 5/10 patients with a favorable profile responded to cDDP. Patients received 70mg/m cDDP every three weeks, CTCs were enumerated and the CTC-cDDP-sensitivity profile was determined. In total, 65 heavily pretreated MBC patients (77% received ≥2 lines of previous chemotherapy for MBC) were eligible for the per-protocol analysis. Primary endpoint was response rate, secondary endpoints included best observed response, progression-free survival (PFS) and overall survival (OS).
RESULTS
The best observed response during cDDP therapy was a partial response in 7% and stable disease in 56% of the patients. None of the patients with a favorable CTC-cDDP-sensitivity profile had a response. The median baseline CTC count was 8 (range 0-3254). Patients with <5 CTCs had a better PFS and OS than patients with ≥5 CTCs (median PFS 4.5 months (95%CI 2.38-6.62) . 2.1 months [(95%CI 1.34-2.80)(=0.009)] and median OS 13.1 months (95%CI 9.89-16.33) . 5.6 months [(95%CI 3.60-7.64)(=0.003)]. No other factors than CTC count were associated with outcome to cDDP therapy, including triple-negative breast cancer versus ER-positive tumors.
CONCLUSIONS
The CTC-cDDP-sensitivity profile was unable to select patients responding to cDDP monotherapy. In an unselected group of heavily pretreated MBC patients, cDDP yields outcomes comparable to other chemotherapeutic regimens for heavily pretreated MBC patients. CTC count was the only factor associated with outcome in these patients.
CLINICAL TRIAL REGISTRATION
(https://www.trialregister.nl/trial/3885, identifier NTR4046).
背景
鉴于顺铂（cDDP）对转移性乳腺癌（MBC）亚型具有铂敏感性且毒性更易于控制，其再次引起了对MBC患者的关注。在此，主要目的是确定循环肿瘤细胞（CTC）的分子特征是否能够识别对cDDP有反应的患者，并描述在一大组接受过蒽环类和紫杉类治疗的MBC患者中cDDP单药治疗的结果。
方法
基于细胞系数据生成了CTC-cDDP敏感性图谱。采用A'Herns单阶段II期设计，如果10名具有良好图谱的患者中有5名对cDDP有反应，则认为进一步研究是值得的。患者每三周接受70mg/m²的cDDP治疗，对CTC进行计数并确定CTC-cDDP敏感性图谱。总共65名经过大量预处理的MBC患者（77%接受过≥2线先前的MBC化疗）符合符合方案分析的条件。主要终点是缓解率，次要终点包括最佳观察到的反应、无进展生存期（PFS）和总生存期（OS）。
结果
在cDDP治疗期间观察到的最佳反应是7%的患者部分缓解，56%的患者疾病稳定。没有一名具有良好CTC-cDDP敏感性图谱的患者有反应。基线CTC计数的中位数为8（范围0-3254）。CTC<5的患者的PFS和OS优于CTC≥5的患者（中位PFS 4.5个月（95%CI 2.38-6.62）对2.1个月[（95%CI 1.34-2.80）（P=0.009）]，中位OS 13.1个月（95%CI 9.89-16.33）对5.6个月[（95%CI 3.60-7.64）（P=0.003）]。除CTC计数外，没有其他因素与cDDP治疗的结果相关，包括三阴性乳腺癌与雌激素受体阳性肿瘤。
结论
CTC-cDDP敏感性图谱无法选择出对cDDP单药治疗有反应的患者。在一组未经选择的经过大量预处理的MBC患者中，cDDP产生的结果与其他用于经过大量预处理的MBC患者的化疗方案相当。CTC计数是这些患者中与结果相关的唯一因素。
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