Is aflibercept an optimal treatment for wt RAS mCRC patients after progression to first line containing anti-EGFR?

Vera, Ruth; Mata, Elena; González, Elena Navarro; Juez, Ignacio; Alonso, Vicente; Iranzo, Patricia Izquierdo; Martínez, Néstor; López, Carlos; Cabrera, José M; Safont, María José; Ruiz-Casado, Ana; Salgado, Mercedes; González, Beatríz; Escudero, P.; Rivera, Fernando; Pericay, Carles

doi:10.1007/s00384-020-03509-x

Cited by 12 publications

(10 citation statements)

References 21 publications

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“…As for safety, 37.5% of the patients reported grade 3–4 toxicities (hematologic 16.6%, hypertension 7.5%, asthenia 5.9%, and perforation 2.5%). Though retrospective, these results were consistent with the VELOUR trial, showing FOLFIRI-aflibercept efficacy was maintained irrespective of prior anti-EGFR treatment, thus suggesting a role for this regimen also in this population ( 96 ). The ongoing, prospectively stratified, biologically enriched, multicenter, phase II DISTINCTIVE study is assessing the efficacy of aflibercept in combination with FOLFIRI in the second-line treatment of RAS WT mCRC patients who received first-line oxaliplatin in combination with an anti-EGFR mAb (either panitumumab or cetuximab); one of the study aims is to prospectively validate VEGFR2 plasma levels as a predictive factor for efficacy of aflibercept in combination with FOLFIRI ( 97 ).…”

Section: Individualized Treatmentsupporting

confidence: 79%

“…These data must be considered with caution due to the retrospective nature of the study, therefore no definitive conclusions can be drawn ( 95 ). In another retrospective study, Vera and colleagues analyzed the efficacy and safety of second-line FOLFIRI-aflibercept in RAS WT mCRC patients resistant to, or who had progressed after, an oxaliplatin plus anti-EGFR regimen ( 96 ). PFS was 6.9 months (95% CI: 6.1–7.8), the ORR was 33% and mOS was 14.5 months (95% CI: 9.7–19.3).…”

Section: Individualized Treatmentmentioning

confidence: 99%

“…Even if none of the mutation subgroups demonstrated significant interaction and though limited by the small sample size, the VELOUR analysis showed also a promising trend for better outcome with aflibercept and FOLFIRI for BRAF MT mCRC patients in OS, PFS and RR. Globally, 36 patients harboring BRAF MT were evaluated; mOS was 10.3 months in the FOLFIRI-aflibercept group versus 5.5 months in the control group (HR: 0.42; 95% CI: 0.16–1.09; p = 0.08) and mPFS was 5.5 versus 2.2 months (HR: 0.59; 95% CI: 0.22–1.58) ( 89 , 96 ). Gelsomino and colleagues conducted a pooled analysis with the aim to assess the impact of anti-angiogenic drugs in patients with pre-treated BRAF MT mCRC.…”

Section: Individualized Treatmentmentioning

confidence: 99%

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Are All Anti-Angiogenic Drugs the Same in the Treatment of Second-Line Metastatic Colorectal Cancer? Expert Opinion on Clinical Practice

2021

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Targeting tumor-driven angiogenesis is an effective strategy in the management of metastatic colorectal cancer (mCRC); however, the choice of second-line therapy is complicated by the availability of several drugs, the occurrence of resistance and the lack of validated prognostic and predictive biomarkers. This review examines the use of angiogenesis-targeted therapies for the second-line management of mCRC patients. Mechanisms of resistance and anti-placental growth factor agents are discussed, and the role of aflibercept, a recombinant fusion protein consisting of portions of human vascular endothelial growth factor receptor (VEGFR)-1 and VEGFR-2, is highlighted. The novel mechanism of action of aflibercept makes it a useful second-line agent in mCRC patients progressing after oxaliplatin-based chemotherapy, as well as in those with resistance after bevacizumab.

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Section: Individualized Treatmentsupporting

confidence: 79%

Section: Individualized Treatmentmentioning

confidence: 99%

Section: Individualized Treatmentmentioning

confidence: 99%

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Are All Anti-Angiogenic Drugs the Same in the Treatment of Second-Line Metastatic Colorectal Cancer? Expert Opinion on Clinical Practice

2021

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“…Treatment-related mortality was 1.6% [34]. A real-world observational study evaluating 120 patients with RAS-WT mCRC who received second-line aflibercept plus FOLFIRI reported hypertension (7.5%), asthenia (5.9%) and perforation (2.5%) as the most frequently occurring [35].…”

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 ceRNA network was constructed based on the hypothesis that lncRNAs directly interact with miRNAs and regulate the activity of mRNAs by acting as miRNA sponges [41]. Based on the associated mRNA, the GO enrichment and KEGG analysis were performed, the results demonstrated that the hub lncRNAs involve in the RAS signaling pathway and transcriptional activator activity, which had been reported in the previous studies [42][43][44]. Moreover, we successfully constructed the LINC00909 overexpression CRC cell lines to veri ed that overexpression LINC00909 could enhance the resistance to the NCRT in CRC.…”

Section: Discussionmentioning

confidence: 69%

LncRNAs Signature Associated with Chemoradiotherapy Response and Prognosis in Locally Advanced Rectal Cancer

Zhang¹,

Guan²,

Wu³

et al. 2021

Preprint

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Background Long non-coding RNAs (lncRNAs) are promising diagnostic and prognostic biomarkers in cancers. Neoadjuvant chemoradiotherapy (NCRT) is the standard of care for patients with locally advanced rectal cancer (LARC). However, studies are limited regarding lncRNAs associated NCRT response and prognosis of LARC patients. This study aimed to identify lncRNAs associated with NCRT response and prognosis in CRC patients, and to explore potential mechanisms. Methods LncRNA expression profiles from our previous gene chip data basing on the LASSO to identify a four-lncRNA signature that predicted NCRT response and prognosis and further validated in 138 colorectal cancer (CRC) patients and 36 LARC patients from our center. A Cox regression model was performed to identify prognostic risk factors. Moreover, we identified the function of the LINC00909 in vivo and in vitro in CRC cell lines. Results Four hub lncRNAs (DBET, LINC00909, FLJ33534, and HSD52) were screened by comparing the relative lncRNA expression of NCRT-responsive and non-responsive patients (AUC = 0.68, 0.73, 0.73, and 0.70, respectively, all p < 0.05). A competing endogenous RNA (ceRNA) network was constructed based on the four lncRNAs. Moreover, the four lncRNAs expression was identified by the external data in cancerous and adjacent non-cancerous tissues in CRC patients. The results demonstrated that the expression of the four lncRNAs was lower in the normal tissues than in the cancerous tissues (all p < 0.05), and the COX analysis demonstrated that the DBET, LINC00909 and FLJ33534 were assocaited with the DFS in CRC patients. The four lncRNAs were also identified in the LARC following NCRT patients, and the result demonstrated that LINC00909 and FLJ33534 had powerful ability to predict the NCRT response and prognosis (all p < 0.05). Basing on the multivariate COX analysis, we constructed a risk score and verified in the CRC and LARC patients in predicting NCRT response and prognosis. Moreover, The expression and prognosis of the DBET, LINC00909 and FLJ33534 in the CRC tissues were identified in the R2 platform and Oncomine database. Moreover, the over-expression LINC00909 cell lines demonstrated that over-expressed the LINC00909 increased the cell lines resistance to the 5-FU and radiotherapy in vivo and in vitro. Conclusion Our findings showed that DBET, LINC00909, and FLJ33534 could serve as novel biomarkers for prediction of NCRT response and prognosis in CRC patients. And LINC00909 could be a novel therapeutic targets in enhancing the NCRT response.

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Is aflibercept an optimal treatment for wt RAS mCRC patients after progression to first line containing anti-EGFR?

Cited by 12 publications

References 21 publications

Are All Anti-Angiogenic Drugs the Same in the Treatment of Second-Line Metastatic Colorectal Cancer? Expert Opinion on Clinical Practice

Are All Anti-Angiogenic Drugs the Same in the Treatment of Second-Line Metastatic Colorectal Cancer? Expert Opinion on Clinical Practice

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

LncRNAs Signature Associated with Chemoradiotherapy Response and Prognosis in Locally Advanced Rectal Cancer

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