Drug updated on 4/17/2024
| Dosage Form | Injection (intravenous; 100 mg/4 mL [25 mg/mL], 200 mg/8 mL [25 mg/mL]) |
| Drug Class | Vascular endothelial growth factor inhibitors |
| Ongoing and Completed Studies | ClinicalTrials.gov |
Indication
- Indicated for use in combination with FOLFIRI (fluorouracil, leucovorin, irinotecan) for the treatment of metastatic colorectal cancer (mCRC) that is resistant to or has progressed following an oxaliplatin regimen.
Summary
- Ziv-aflibercept (Zaltrap) is a recombinant fusion protein that serves as a decoy receptor for vascular endothelial growth factors. It is used in combination with FOLFIRI for second-line salvage chemotherapy in metastatic colorectal cancer following resistance or progression after an oxaliplatin regimen.
- Seven systematic reviews/meta-analyses were analyzed to gather information about the safety and effectiveness of Zaltrap compared to other therapies.
- When combined with FOLFIRI, Zaltrap exhibits significant antiangiogenic adverse events such as grade III/IV hypertension, proteinuria, and hemorrhagic events more frequently than control treatments. Additionally, it shows an increased risk of hypertension and proteinuria compared to other biological agents like bevacizumab, ramucirumab, and regorafenib.
- Despite these safety concerns, studies indicate that Zaltrap offers improved efficacy over chemotherapy alone or FOLFIRI alone in terms of progression-free survival (PFS), overall survival (OS), and objective response rate (ORR). This makes it a competitive option against medications such as regorafenib and bevacizumab, particularly in the second-line treatment setting for metastatic colorectal cancer (mCRC).
- The safety profile does not notably differ based on the treatment line or chemotherapy regime, indicating consistency across different subgroups. However, high-grade adverse events associated with this drug include neutropenia and venous thromboembolic events, along with common side effects like diarrhea, weakness, stomatitis, etc.
- Economic analyses have raised concerns regarding the cost-effectiveness of ziv-aflibercept (Zaltrap) compared to FOLFIRI alone or other biological options within the mCRC treatment landscape. This is due to a lack of cost advantage despite its favorable effect on tumor response and survival metrics, which complicates the overall clinical value proposition.
Product Monograph / Prescribing Information
| Document Title | Year | Source |
|---|---|---|
| Zaltrap (ziv-aflibercept) Prescribing Information. | 2020 | Sanofi-Aventis U.S. LLC, Bridgewater, NJ |
Systematic Reviews / Meta-Analyses
Clinical Practice Guidelines
| Document Title | Year | Source |
|---|---|---|
| Rectal cancer, version 2.2022, NCCN clinical practice guidelines in oncology. | 2022 | Journal of the National Comprehensive Cancer Network |
| Clinical management of metastatic colorectal cancer in the era of precision medicine. | 2022 | CA: A Cancer Journal for Clinicians |
| Treatment of patients with late-stage colorectal cancer: ASCO resource-stratified guideline. | 2020 | Journal of Clinical Oncology |
| Treatment sequencing in metastatic colorectal cancer. | 2019 | European Journal of Cancer |