Abstract

BackgroundBoth aflibercept and bevacizumab-based regimens are available II-line treatment options for patients with metastatic colorectal cancer (mCRC). However, no head-to-head trials established the optimal anti-angiogenic strategy for this setting.MethodsWe launched a multicenter, retrospective, observational study to assess and compare clinical efficacy of aflibercept-based and bevacizumab-based regimens as II-line treatment for patients with mCRC. Patients with KRAS/NRAS/BRAF-wild type and KRAS/NRAS mutant tumors were also analyzed separately.Findings348 consecutive patients were included, of whom 153 and 195 were treated with bevacizumab- and aflibercept-based regimens, respectively. The median age of the study population was 64 years, with 54.6% of males, 31.6% with ECOG-PS ≥1, and 62.9% with left-sided primary tumors. Overall, 81.9% underwent prior primary tumor resection, 61.5% had ≥2 metastatic sites and 30.7% had peritoneal disease. Patients treated with aflibercept showed an increased risk of death (corrected [co]-HR 1.92, 95%CI: 1.37-2.68), of disease progression/death (co-HR 1.43, 95%CI: 1.12-1.82) and a decreased objective response rate (ORR) (21.5% vs 34.7%, p=0.007) in comparison to bevacizumab. Of note, patients treated with II-line bevacizumab were more frequently treated in the third line setting after disease progression (91.1% vs 68.5%). Among the 242 patients included in the KRAS/NRAS mutant cohort, treatment with bevacizumab was associated with longer overall survival (OS) (18.0 months vs 12.5 months, p=0.0069), but similar progression free survival (PFS) (p=0.32) and ORR (p=0.57). Among the 80 patients included in the KRAS/NRAS, BRAF wild type cohort, patients treated with bevacizumab achieved significantly longer OS (20.2 months vs 10.6 months, p=0.013), PFS (8.4 months vs 3.7 months, p=0.0002), and higher ORR (48.6% vs 15.0%, p=0.0016), compared to those treated with aflibercept. All the results were independently confirmed with inverse probability of treatment weighting and with fixed multivariable Cox regressions.ConclusionThese findings seem to support the use of bevacizumab-based over aflibercept-based regimens as II-line treatment of patients with mCRC, especially in those with KRAS/NRAS and BRAF wild type tumors.Micro abstractAflibercept- and bevacizumab-based regimens are two valuable second-line (II-line) treatment options for metastatic colorectal cancer (mCRC). However, no head-to-head trials have compared these anti-angiogenic strategies in this setting. This multicenter, retrospective, observational study assessed the clinical efficacy of these regimens. A total of 348 patients were included: 153 treated with bevacizumab-based regimens and 195 treated with aflibercept-based regimens. The findings support the use of bevacizumab-based regimens, particularly in patients with RAS/BRAF wild-type tumors.