Department of Medical Oncology, Franco-British Hospital-Fondation Cognacq-Jay, Levallois-Perret, France.
Statistical Unit, Aide et Recherche en Cancérologie Digestive, Foundation, Levallois-Perret, France.
JAMA Netw Open. 2020 Oct 1;3(10):e2020425. doi: 10.1001/jamanetworkopen.2020.20425.
In the pivotal Bevacizumab-Avastin Adjuvant (AVANT) trial, patients with high-risk stage II colon cancer (CC) had 5-year and 10-year overall survival (OS) rates of 88% and 75%, respectively, with adjuvant fluorouracil and oxaliplatin-based chemotherapy; however, the trial did not demonstrate a disease-free survival (DFS) benefit of adding bevacizumab to oxaliplatin-based chemotherapy in stage III CC and suggested a detrimental effect on OS. The Long-term Survival AVANT (S-AVANT) study was designed to collect extended follow-up for patients in the AVANT trial.
To explore the efficacy of adjuvant bevacizumab combined with oxaliplatin-based chemotherapy in patients with high-risk, stage II CC.
DESIGN, SETTING, AND PARTICIPANTS: This prespecified secondary end point analysis of the AVANT and S-AVANT studies included 573 patients with curatively resected high-risk stage II CC and at least 1 of the following criteria: stage T4, bowel obstruction or perforation, blood and/or lymphatic vascular invasion and/or perineural invasion, age younger than 50 years, or fewer than 12 nodes analyzed. The AVANT study was a multicenter randomized stage 3 clinical trial. Data were collected from December 2004 to February 2019, and data for this study were analyzed from March to September 2019.
Patients were randomly assigned to receive 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX4), FOLFOX4 with bevacizumab, or capecitabine and oxaliplatin (XELOX) with bevacizumab.
The primary end points of this secondary analysis were DFS and OS in patients with high-risk stage II CC.
The AVANT study included 3451 patients, of whom 573 (16.6%) had high-risk stage II CC (192 [33.5%] randomized to FOLFOX4 group; 194 [33.9%] randomized to FOLFOX4 with bevacizumab group; 187 [32.6%] randomized to XELOX with bevacizumab group). With a median (interquartile range) age of 57.0 (47.2-65.7) years, the study population comprised 325 men (56.7%) and 248 women (43.3%). After a median (interquartile range) follow-up of 6.9 (6.1-11.3) years, the 3-year DFS and 5-year OS rates were 88.2% (95% CI, 83.7%-93.0%) and 89.7% (95% CI, 85.4%-94.2%) in the FOLFOX4 group, 86.6% (95% CI, 81.8%-91.6%) and 89.7% (95% CI, 85.4%-94.2%) in the FOLFOX4 with bevacizumab group, and 86.7% (95% CI, 81.8%-91.8%) and 93.2% (95% CI, 89.6%-97.0%) in the XELOX with bevacizumab group, respectively. The DFS hazard ratio was 0.94 (95% CI, 0.59-1.48; P = .78) for FOLFOX4 with bevacizumab vs FOLFOX4 and 1.07 (95% CI, 0.69-1.67; P = .76) for XELOX with bevacizumab vs FOLFOX4. The OS hazard ratio was 0.92 (95% CI, 0.55-1.55; P = .76) for FOLFOX4 with bevacizumab vs FOLFOX4 and 0.85 (95% CI, 0.50-1.44; P = .55) for XELOX with bevacizumab vs FOLFOX4.
In this secondary analysis of data from the AVANT trial, adding bevacizumab to oxaliplatin-based chemotherapy was not associated with longer DFS or OS in patients with high-risk stage II CC. The findings suggest that the definition of high-risk stage II CC needs to be revisited.
ClinicalTrial.gov Identifiers: AVANT (NCT00112918); S-AVANT (NCT02228668).
在关键性贝伐珠单抗-阿瓦斯汀（AVANT）试验中，高风险 II 期结肠癌（CC）患者的 5 年和 10 年总生存率（OS）分别为 88%和 75%，采用氟尿嘧啶和奥沙利铂为基础的辅助化疗；然而，该试验并未显示在 III 期 CC 中添加贝伐珠单抗到奥沙利铂为基础的化疗中可改善无病生存率（DFS），并提示对 OS 有不利影响。长期生存 AVANT（S-AVANT）研究旨在为 AVANT 试验中的患者收集扩展随访数据。
探讨辅助贝伐珠单抗联合奥沙利铂为基础的化疗在高风险 II 期 CC 患者中的疗效。
设计、地点和参与者：这是 AVANT 和 S-AVANT 研究的次要终点分析，纳入了 573 例接受根治性切除的高风险 II 期 CC 且至少符合以下标准之一的患者：T4 期、肠梗阻或穿孔、血管和/或淋巴管侵犯和/或神经周围侵犯、年龄小于 50 岁或分析的淋巴结少于 12 个。AVANT 研究是一项多中心随机 III 期临床试验。数据收集于 2004 年 12 月至 2019 年 2 月，本研究的数据分析于 2019 年 3 月至 9 月进行。
患者被随机分配接受 5-氟尿嘧啶、亚叶酸钙和奥沙利铂（FOLFOX4）、FOLFOX4 联合贝伐珠单抗或卡培他滨和奥沙利铂（XELOX）联合贝伐珠单抗。
本次二次分析的主要终点为高风险 II 期 CC 患者的 DFS 和 OS。
AVANT 研究共纳入 3451 例患者，其中 573 例（16.6%）为高风险 II 期 CC（192 例[33.5%]随机分配至 FOLFOX4 组；194 例[33.9%]随机分配至 FOLFOX4 联合贝伐珠单抗组；187 例[32.6%]随机分配至 XELOX 联合贝伐珠单抗组）。研究人群的中位（四分位距）年龄为 57.0（47.2-65.7）岁，包括 325 名男性（56.7%）和 248 名女性（43.3%）。中位（四分位距）随访 6.9（6.1-11.3）年后，FOLFOX4 组的 3 年 DFS 和 5 年 OS 率分别为 88.2%（95%CI，83.7%-93.0%）和 89.7%（95%CI，85.4%-94.2%），FOLFOX4 联合贝伐珠单抗组分别为 86.6%（95%CI，81.8%-91.6%）和 89.7%（95%CI，85.4%-94.2%），XELOX 联合贝伐珠单抗组分别为 86.7%（95%CI，81.8%-91.8%）和 93.2%（95%CI，89.6%-97.0%）。FOLFOX4 联合贝伐珠单抗组与 FOLFOX4 组相比，DFS 风险比为 0.94（95%CI，0.59-1.48；P=0.78），XELOX 联合贝伐珠单抗组与 FOLFOX4 组相比，DFS 风险比为 1.07（95%CI，0.69-1.67；P=0.76）。FOLFOX4 联合贝伐珠单抗组与 FOLFOX4 组相比，OS 风险比为 0.92（95%CI，0.55-1.55；P=0.76），XELOX 联合贝伐珠单抗组与 FOLFOX4 组相比，OS 风险比为 0.85（95%CI，0.50-1.44；P=0.55）。
在 AVANT 试验的二次分析中，在奥沙利铂为基础的化疗中添加贝伐珠单抗并未延长高风险 II 期 CC 患者的 DFS 或 OS。这些发现表明需要重新定义高风险 II 期 CC 的定义。
AVANT（NCT00112918）；S-AVANT（NCT02228668）。
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