University Hospital of Ourense, Ourense, Spain.
University Hospital of A Coruña, A Coruña, Spain.
Cancer Med. 2019 Mar;8(3):882-889. doi: 10.1002/cam4.1903. Epub 2019 Jan 28.
The phase III VELOUR trial demonstrated efficacy with combined FOLFIRI-aflibercept in patients with metastatic colorectal cancer previously treated with oxaliplatin with or without bevacizumab versus placebo. The effect of FOLFIRI-aflibercept in routine clinical practice was evaluated.
METHODS/PATIENTS: Overall survival (OS), progression-free survival (PFS), response and safety were analysed for 78 patients treated with FOLFIRI-aflibercept at six GITuD institutions. Exploratory analyses of prognostic and predictive markers of efficacy were performed.
Patients had good general status (PS 0-1 96.2%), tumours were mostly RAS-mutant (75.6%), synchronous (71.8%), and left-sided (71.8%). Prior therapy included bevacizumab (47.4%) and anti-EGFR agents (12.8%). PFS was longer for metachronous than synchronous tumours (11.0 vs 5.0 months, P = 0.028), and for left-colon tumours (7.0 vs 3.0 months, P = 0.044). RAS-mutant status, first-line treatment and primary tumour surgery did not impact PFS. The disease control rate was 70.5%. The most common grade 3/4 toxicities were neutropenia (15.3%), asthenia (10.3%), diarrhea and mucositis (6.4% each). Dysphonia was reported in 39.7% of patients, and grade 3 hypertension in 3.8%. Development of hypertension (any grade) was significantly associated with a reduced risk of progression by multivariate analysis (HR = 2.7; 95%CI 1.3-5.4; P = 0.001).
Efficacy with FOLFIRI-aflibercept in a real-life population was in line with results from the pivotal trial and toxicity was manageable with treatment adaptation. Survival outcomes were not impacted by primary tumour location, RAS-mutant status, first-line treatment or primary tumour surgery. Hypertension may be a surrogate marker of efficacy in this patient population.
III 期 VELOUR 试验表明，在既往接受奥沙利铂联合或不联合贝伐珠单抗治疗的转移性结直肠癌患者中，联合 FOLFIRI-阿柏西普治疗具有疗效，而安慰剂则没有。评估了 FOLFIRI-阿柏西普在常规临床实践中的效果。
方法/患者：对 6 家 GITuD 机构的 78 例接受 FOLFIRI-阿柏西普治疗的患者进行了总生存期（OS）、无进展生存期（PFS）、反应和安全性分析。对疗效的预测和预后标志物进行了探索性分析。
患者一般状况良好（PS 0-1 96.2%），肿瘤多为 RAS 突变（75.6%），同步（71.8%），左半结肠（71.8%）。既往治疗包括贝伐珠单抗（47.4%）和抗 EGFR 药物（12.8%）。与同步肿瘤相比，异时性肿瘤的无进展生存期更长（11.0 个月比 5.0 个月，P=0.028），左结肠癌的无进展生存期更长（7.0 个月比 3.0 个月，P=0.044）。RAS 突变状态、一线治疗和原发肿瘤手术对无进展生存期没有影响。疾病控制率为 70.5%。最常见的 3/4 级毒性为中性粒细胞减少（15.3%）、乏力（10.3%）、腹泻和黏膜炎（各 6.4%）。39.7%的患者出现声音嘶哑，3.8%的患者出现 3 级高血压。多因素分析显示，高血压的发生（任何级别）与进展风险降低显著相关（HR=2.7；95%CI 1.3-5.4；P=0.001）。
在真实人群中，FOLFIRI-阿柏西普的疗效与关键试验的结果一致，并且毒性通过治疗适应是可以控制的。生存结果不受原发肿瘤位置、RAS 突变状态、一线治疗或原发肿瘤手术的影响。在该患者人群中，高血压可能是疗效的替代标志物。
