Retrospective evaluation of FOLFIRI3 alone or in combination with bevacizumab or aflibercept in metastatic colorectal cancer

Abstract

BACKGROUND The treatment of metastatic colorectal cancer (mCRC) relies of chemotherapy. The efficacy of the standard FOLFIRI-therapy could be improved by a modification of the regimen by splitting the dose of irinotecan on day 1 and day 3 in the FOLFIRI3 regimen. AIM To determine safety and efficacy of FOLFIRI3 regimen. METHODS This is a monocentric retrospective study evaluating the efficacy and safety of the FOLFIRI3 regimen given alone or in combination with bevacizumab or aflibercept in patients with previously treated mCRC. RESULTS One hundred and fifty-three consecutive patients were included (18 treated with FOLFIRI3, 99 with FOLFIRI3 plus bevacizumab and 36 with FOLFIRI3 plus aflibercept). The overall response rate (ORR) and disease control rate were 51% and 62%, respectively. Similar ORRs were observed in all 3 cohorts. Median progression-free survival (PFS) and overall survival (OS) were 3.9 mo (95%CI: 3.2-4.9) and 9.4 mo (95%CI: 6.6-12), respectively. Median PFS and OS values were improved in the FOLFIRI3 plus aflibercept group. The most common grade 3-4 adverse events were diarrhoea (21.6%) and neutropenia (11.8%), and these toxicities were more frequent in the FOLFIRI3 plus aflibercept group. According to the multivariate Cox proportional model, previous surgery of metastasis and aflibercept were associated with outcomes. CONCLUSION The modification of the FOLFIRI regimen impacted treatment response of mCRC patients. The addition of an antiangiogenic agent, in particular aflibercept, enhanced the clinical benefit and improved survival.

Efficacy and safety of aflibercept plus chemotherapy in metastatic colorectal cancer: A systematic review and PRISMA‐Compliant single‐arm Meta‐Analysis of noncomparative clinical studies and randomized controlled trials

“…This meta-analysis showed that the incidence of grade III [40][41][42][43] also support the view that the incidence of adverse reactions and serious adverse reactions of aflibercept plus chemotherapy was higher than that of chemotherapy alone and other anti-VEGF drugs plus chemotherapy. The adverse reactions of aflibercept plus chemotherapy have become an important factor limiting its application.…”

“…The results of two meta‐analysis 47,48 also showed that the incidence of proteinuria (All levels: RR 1.85, 95%CI 1.63–2.11; Advanced: RR 2.37, 95% CI 1.84–3.05) and hypertension (All grades: OR 1.93, 95% CI 1.61–2.32, p < 0.001; Advanced: OR 2.06, 95% CI 1.79–2.37, p < 0.001) of aflibercept plus chemotherapy was higher than that of bevacizumab plus chemotherapy. The results of several observational studies 40‐43 also support the view that the incidence of adverse reactions and serious adverse reactions of aflibercept plus chemotherapy was higher than that of chemotherapy alone and other anti‐VEGF drugs plus chemotherapy. The adverse reactions of aflibercept plus chemotherapy have become an important factor limiting its application.…”

“…A retrospective study 41 of 74 patients with RAS mutant metastatic colorectal cancer concluded that in the second‐line treatment, compared with bevacizumab plus chemotherapy, aflibercept plus chemotherapy had lower risk of death. The results of the other two observational studies 42,43 also supported that the efficacy of aflibercept plus chemotherapy was better than bevacizumab plus chemotherapy in the second‐line treatment of mCRC. In mCRC patients with bevacizumab‐resistant, aflibercept plus chemotherapy might be an optional second‐line therapy.…”

“…Several observational studies [40][41][42][43] had compared the efficacy of aflibercept plus chemotherapy and bevacizumab plus chemotherapy in the treatment of mCRC, but the conclusions were different.…”

Safety of Aflibercept in Metastatic Colorectal Cancer: A Literature Review and Expert Perspective on Clinical and Real-World Data

“…One monocentric retrospective study evaluated the FOLFIRI3 regimen given alone (n = 18) or in combination with bevacizumab (n = 99) or aflibercept (n = 36) in French patients with previously treated mCRC. The most frequent grade 3/4 AEs in the aflibercept plus FOLFIRI3 were diarrhea (33%) and neutropenia (14%) [37]. The AGEO study evaluated aflibercept plus chemotherapy beyond second-line therapy in patients with mCRC.…”