Charité Universitätsmedizin Berlin, Campus Virchow Klinikum, Department of Medical Oncology and Hematology, Berlin, Germany; Universitätsklinikum Hamburg-Eppendorf, Department of Medical Oncology, Hamburg, Germany.
University of Göttingen, Department of General, Visceral and Pediatric Surgery, Göttingen, Germany.
Eur J Cancer. 2020 Oct;138:172-181. doi: 10.1016/j.ejca.2020.06.032. Epub 2020 Sep 2.
CONKO-006 was designed for patients with pancreatic adenocarcinoma with postsurgical R1 residual status to evaluate the efficacy and safety of the combination of gemcitabine and sorafenib (GemSorafenib) compared with those of gemcitabine + placebo (GemP) for 12 cycles.
This randomised, double-blind, placebo-controlled, multicenter study was planned to detect an improvement in recurrence-free survival (RFS) from 42% to 60% after 18 months. Secondary objectives were overall survival (OS), safety and duration of treatment.
122 patients were included between 02/2008 and 09/2013; 57 were randomised to GemSorafenib and 65 to GemP. Patient characteristics were wellbalanced (GemSorafenib/GemP) in terms of median age (63/63 years), tumour size (T3/T4: 97/97%), and nodal positivity (86/85%). Grade 3/4 toxicities comprised diarrhoea (GemSorafenib: 12%; GemP: 2%), elevated gamma-glutamyl transferase (GGT) (19%; 9%), fatigue (5%; 2%) and hypertension (5%; 2%), as well as neutropenia (18%; 25%) and thrombocytopenia (9%; 2%). By August 2017, 118 (97%) RFS event had occurred. There were no difference in RFS (median GemSorafenib: 8.5 versus GemP: 9.4 months; p = 0.730) nor OS (median GemSorafenib: 17.6 versus GemP: 17.5 months; p = 0.481). Landmark analyses suggest that patients who received more than six cycles of postoperative chemotherapy had significantly longer OS (p = 0.021).
CONKO-006 is the first randomised clinical trial to include exclusively patients with PDAC with postsurgical R1 status thus far. Sorafenib added to gemcitabine did neither improve RFS nor OS. However, postoperative treatment exceeding six months seemed to prolong survival and should be further investigated in these high-risk patients.
German Tumor Study Registry (Deutsches Krebsstudienregister), DRKS00000242.
CONKO-006 旨在评估吉西他滨联合索拉非尼（GemSorafenib）与吉西他滨联合安慰剂（GemP）在 12 个周期内用于治疗术后 R1 残留状态的胰腺腺癌患者的疗效和安全性。
这是一项随机、双盲、安慰剂对照、多中心研究，旨在检测 18 个月后无复发生存率（RFS）从 42%提高到 60%。次要终点是总生存期（OS）、安全性和治疗持续时间。
2008 年 2 月至 2013 年 9 月期间共纳入 122 例患者；57 例随机分配至 GemSorafenib 组，65 例分配至 GemP 组。患者特征在中位年龄（63/63 岁）、肿瘤大小（T3/T4：97/97%）和淋巴结阳性率（86/85%）方面均得到良好平衡。3/4 级毒性包括腹泻（GemSorafenib：12%；GemP：2%）、γ-谷氨酰转移酶（GGT）升高（19%；9%）、疲劳（5%；2%）和高血压（5%；2%），以及中性粒细胞减少症（18%；25%）和血小板减少症（9%；2%）。截至 2017 年 8 月，118 例（97%）发生 RFS 事件。RFS 无差异（GemSorafenib 中位值：8.5 个月 vs GemP 中位值：9.4 个月；p=0.730），OS 也无差异（GemSorafenib 中位值：17.6 个月 vs GemP 中位值：17.5 个月；p=0.481）。里程碑分析表明，接受术后化疗超过 6 个周期的患者 OS 显著延长（p=0.021）。
CONKO-006 是迄今为止唯一一项纳入术后 R1 状态胰腺腺癌患者的随机临床试验。吉西他滨联合索拉非尼既不能提高 RFS，也不能提高 OS。然而，超过 6 个月的术后治疗似乎延长了生存时间，应在这些高危患者中进一步研究。
德国肿瘤研究注册处（Deutsches Krebsstudienregister），DRKS00000242。
