FOLFIRI3-aflibercept in previously treated patients with metastatic colorectal cancer

Carola, Candice; Ghiringhelli, François; Kim, Stéfano; Thewis, André; Barlet, Juliette; Bengrine-Lefèvre, Léïla; Garcia-Larnicol, Marie-Line; Borg, Christophe; Daınese, Linda; Steuer, Nils; Richa, Hubert; Benetkiewicz, Magdalena; Larsen, Annette K.; Gramont, Aimery de; Chibaudel, Benoist

doi:10.5306/wjco.v9.i5.110

Cited by 9 publications

(5 citation statements)

References 19 publications

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“…The frequency of severe diarrhoea was also more prevalent than what has been previously reported in the VELOUR study, where only 19% of patients had grade 3 or higher diarrhoea[8]. A similar level of diarrhoea was observed in the recent retrospective study of Carola, in which 38% of patients experienced severe diarrhoea events[14]. Our group previously reported the association between severe diarrhoea induced by aflibercept and microscopic colitis[15,16].…”

Section: Discussionsupporting

confidence: 68%

“…Importantly, these results did not differ from the FOLFIRI3 results without a targeted therapy[13]. A recent retrospective report on the usage of FOLFIRI3 in combination with aflibercept demonstrated a response rate of 35%[14]. Results were improved in irinotecan-naïve patients in comparison to the irinotecan-experienced cohort with median PFS and OS of 11.3 mo and 17.0 mo, respectively, for the irinotecan-naïve group and 5.7 mo and 14.3 mo for the irinotecan-experienced group.…”

Section: Discussionmentioning

confidence: 90%

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

Devaux

Gérard

Richard

et al. 2019

WJCO

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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.

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Section: Discussionsupporting

confidence: 68%

Section: Discussionmentioning

confidence: 90%

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

Devaux

Gérard

Richard

et al. 2019

WJCO

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“…In a French study evaluating FOLFIRI3-aflibercept in 65 evaluable patients with previously treated mCRC, the most frequently reported grade 3/4 AEs were diarrhea (30.8%), neutropenia (7.7%), hypertension (3.2%) and stomatitis (9.2%) ( Figure 4) [36]. 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.…”

Section: European and The Us Studiesmentioning

confidence: 99%

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

Muro

Salinardi

Singh

et al. 2020

Cancers

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Background: Metastatic colorectal cancer (mCRC) represents a substantial health burden globally and an increasing challenge in Asian countries. Treatment options include chemotherapy plus a vascular endothelial growth factor (VEGF) inhibitor (such as bevacizumab, aflibercept or ramucirumab), or anti-epidermal growth factor receptor (EGFR) therapies. Aflibercept, a recombinant fusion protein, has been approved for treatment of mCRC in combination with FOLFIRI for patients whose disease progresses during or after treatment with an oxaliplatin-containing regimen, based on its efficacy and tolerability profile in clinical trials. This report aims to provide an overview of both clinical and real-world evidence and experience on the use of aflibercept in routine clinical practice, with a focus on European, American and Asian populations. Methods: A literature search was conducted in PubMed (on 28th February 2019) using the search terms ("aflibercept") and ("Colorectal"OR"CRC") to identify publications containing information on aflibercept-containing regimens. Results: The adverse events (AE) profile was similar between geographical locations. Across trials, real-world and retrospective studies, grade ≥ 3 hypertension and proteinuria were amongst the most frequently reported AEs. Conclusions: The safety profile of aflibercept is generally manageable and comparable across various geographic locations.

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“…The dose escalation of irinotecan was limited by diarrhea toxicity in this phase 1 study during the DLT period, which was defined as the first 2 cycles of the FOLFIRINOX 3-bevacizumab regimen. These findings are unsurprising, and previous reports of FOLFIRI3 have described grade 3-4 diarrhea toxicity in around 30% of patients [30][31][32]. Other major adverse events included asthenia in 92% of cases, and grade 1-2 nausea/vomiting in 61.5%.…”

Section: Discussionmentioning

confidence: 80%

Phase I Dose-Escalation Trial of an Innovative Chemotherapy Regimen Combining a Fractionated Dose of Irinotecan Plus Bevacizumab, Oxaliplatin, 5-Fluorouracil, and Folinic Acid (bFOLFIRINOX-3) in Chemorefractory Metastatic Colorectal Cancer

Bellio

Bertaut

Hervieu

et al. 2021

Cancers

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The care of metastatic colorectal cancers is based on combination chemotherapies including 5-fluorouracil, oxaliplatin, irinotecan, and monoclonal antibodies targeting the epidermal growth factor receptor or vascular endothelial growth factor. The regimen is determined based on the patient’s molecular biology and general condition. Irinotecan bifractionation showed efficacy in chemorefractory patients in a previous study, FOLFIRI-3, but a desynchronized triplet has never been tested. The aim of bFOLFIRINOX-3 is to determine the safety, tolerance, and efficacy of a new regimen (FOLFIRINOX-3 bevacizumab) in chemorefractory patients. The aim of this study was to evaluate the safety and efficacy of FOLFIRINOX-3 bevacizumab in chemorefractory metastatic colorectal cancer (mCRC). A standard phase I, “3 + 3” design study was performed. The standard protocol comprised simplified FOLFOX 4 (folinic acid 400 mg/m2), 5-fluorouracil (a 400 mg/m2 bolus followed by 2400 mg/m2 for 46 h), oxaliplatin (85 mg/m2) and irinotecan (administered before and after 5-fluorouracil infusion), plus bevacizumab (5 mg/kg). In a “3 + 3” design, three different doses of irinotecan were tested: 60, 70 and 90 mg/m2. The primary endpoint was the maximum tolerable dose (MTD) of irinotecan. The secondary endpoints included the objective response (at 8 and 16 weeks) according to the RECIST 1.1 criteria and progression free survival. Thirteen patients were enrolled, and twelve patients were finally evaluated for dose-limiting toxicity (DLT). The dose level defined was 70 mg/m2 irinotecan. A total of three DLTs were observed (grade 3 diarrhea): two DLTs at the 90 mg/m2 dose level and one at the 70 mg/m2 dose level. The most frequently described adverse events were asthenia (93%), diarrhea (77%), nausea (62%) and peripheral sensory neuropathy (46%). The most frequent biological event was thrombopenia (54%). Regarding efficacy, among the 11 evaluable patients, no progression was observed at 8 weeks, and the partial response rate was 18.2%. At 16 weeks, a partial response rate of 27.3% was observed, and five patients had a stable disease. The new regimen of bFOLFIRINOX-3 with irinotecan at 70 mg/m2 was well tolerated. In chemorefractory patients, this protocol shows a high response rate.

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FOLFIRI3-aflibercept in previously treated patients with metastatic colorectal cancer

Cited by 9 publications

References 19 publications

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

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

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

Phase I Dose-Escalation Trial of an Innovative Chemotherapy Regimen Combining a Fractionated Dose of Irinotecan Plus Bevacizumab, Oxaliplatin, 5-Fluorouracil, and Folinic Acid (bFOLFIRINOX-3) in Chemorefractory Metastatic Colorectal Cancer

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