Antiangiogenic therapy for refractory colorectal cancer: current options and future strategies
Rachel Riechelmann1, Axel Grothey2
1Instituto do Cancer do Estado de São Paulo, Av. Doutor Arnaldo 251, 5° Andar, CEP 01246-000, São Paulo, SP, Brazil.
Abstract:
Even though significant improvements in the treatment of colorectal cancer (CRC) have been made in recent years, survival rates for metastatic colorectal cancer (mCRC) are poor. Effective treatment options for metastatic colorectal cancer remain limited, and new therapeutic strategies are desperately needed. Several tyrosine kinase inhibitors (TKIs) and monoclonal antibodies (mAbs) that target angiogenesis, a critical process for facilitating tumor cell growth, invasion, and metastasis, are either approved or in clinical development for the treatment of mCRC. Many of these agents have shown efficacy in mCRC, both as single agents and in combination with standard chemotherapy regimens. However, there is a need for predictive markers of response to identify those patients most likely to benefit from antiangiogenic therapy, and, to date, no markers of this type have been validated in patients. Additionally, because antiangiogenic agents typically cause cytostatic as opposed to cytotoxic antitumor effects, it is important to determine the best strategies for evaluating therapeutic response in mCRC to ensure maximum clinical benefit. In this review, we summarize the efficacy and tolerability of approved and investigational antiangiogenic agents for the treatment of mCRC. We also discuss potential markers of response to antiangiogenic agents and how these markers, along with appropriate endpoint selection, can improve clinical trial design.
Insights
New antiangiogenic therapies show promise for metastatic colorectal cancer (mCRC). Identifying predictive response markers and optimal endpoints is crucial for improving treatment efficacy and clinical trial design in mCRC.
Area of Science:
- Oncology
- Cancer Research
- Pharmacology
Background:
- Metastatic colorectal cancer (mCRC) has poor survival rates despite treatment advances.
- Limited effective therapies necessitate novel therapeutic strategies for mCRC.
- Antiangiogenic agents targeting tumor angiogenesis are a key focus in mCRC treatment.
Purpose of the Study:
- To review the efficacy and tolerability of approved and investigational antiangiogenic agents for mCRC.
- To discuss potential predictive markers for patient response to antiangiogenic therapy.
- To explore strategies for evaluating therapeutic response and improving clinical trial design.
Main Methods:
- Literature review of antiangiogenic agents (tyrosine kinase inhibitors and monoclonal antibodies) in mCRC.
- Analysis of clinical trial data on efficacy, tolerability, and response markers.
- Discussion of challenges in assessing cytostatic effects and selecting appropriate endpoints.
Main Results:
- Several antiangiogenic agents demonstrate efficacy in mCRC, as monotherapy or in combination with chemotherapy.
- Validated predictive markers for antiangiogenic therapy response in mCRC are currently lacking.
- Current methods for evaluating therapeutic response may need adaptation for cytostatic agents.
Conclusions:
- Antiangiogenic agents represent a significant advancement in mCRC treatment, but patient selection remains a challenge.
- Development and validation of predictive biomarkers are essential for personalized antiangiogenic therapy.
- Optimized clinical trial designs incorporating appropriate endpoints are needed to maximize patient benefit.
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