Targeted therapy attacking cancer cells

Targeted Therapies: A Ray of Hope in Advanced Colorectal Cancer

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Jordan Keane in Health & Wellness December 2025 • 4 min read.

"Unlocking the potential of conversion therapy to improve outcomes in mCRC patients."


Colorectal cancer (CRC) remains a significant global health challenge, with a subset of patients presenting with initially unresectable or borderline resectable metastatic disease (mCRC). In these cases, the primary goal shifts towards converting the tumor to a resectable state through systemic therapy, a strategy known as conversion therapy.

Chemotherapy (CT) has long been the cornerstone of conversion therapy, but the advent of targeted therapies has opened new avenues for improving treatment outcomes. These targeted agents, such as anti-EGFR and anti-VEGF antibodies, work by specifically inhibiting key pathways involved in cancer growth and spread, offering the potential to enhance the effectiveness of chemotherapy.

This article delves into the role of targeted therapies in conversion therapy for mCRC, drawing upon a systematic review and meta-analysis of randomized controlled trials (RCTs). We will explore the benefits and risks associated with combining targeted therapies with chemotherapy, providing insights into how these strategies can improve resection rates, survival outcomes, and patient safety.

Anti-EGFR vs Anti-VEGF: Which Targeted Therapy Reigns Supreme?

Targeted therapy attacking cancer cells

The meta-analysis compared the efficacy of anti-EGFR and anti-VEGF therapies when combined with chemotherapy in mCRC patients. While the results showed no statistically significant difference in RO resection rates between the two groups, there was a trend towards better outcomes with anti-EGFR + CT (RR 1.44, p = 0.1156). Similarly, objective response rates (ORR) were comparable between the two groups (RR 1.05, p = 0.6039).

However, a significant difference emerged in overall survival (OS), with patients receiving anti-EGFR + CT experiencing longer survival compared to those receiving anti-VEGF + CT (HR: 0.64, p = 0.0036). Progression-free survival (PFS), on the other hand, was numerically better in the anti-EGFR + CT group, although this difference did not reach statistical significance.

  • RO Resection Rate: Anti-EGFR + CT showed a trend towards better RO resection rates compared to anti-VEGF + CT, though not statistically significant.
  • Objective Response Rate (ORR): Similar ORR were observed between the two groups.
  • Overall Survival (OS): Anti-EGFR + CT resulted in significantly longer OS compared to anti-VEGF + CT.
  • Progression-Free Survival (PFS): PFS was numerically better in the anti-EGFR + CT group.
These findings suggest that anti-EGFR therapies may offer a survival advantage over anti-VEGF therapies in the context of conversion therapy for mCRC. However, it is important to note that these results are based on a meta-analysis of RCTs, and further research is needed to confirm these findings and identify the specific patient populations that may benefit most from each approach.

Balancing Efficacy and Safety: A Word of Caution

While targeted therapies offer promising benefits in conversion therapy for mCRC, it is crucial to consider their potential side effects. The meta-analysis revealed that anti-EGFR + CT was associated with a significantly greater incidence of adverse events compared to CT alone (RR: 1.26, p < 0.0001).

Therefore, treatment decisions should be made on a case-by-case basis, carefully weighing the potential benefits and risks of each approach. Factors such as tumor location, KRAS mutation status, and patient comorbidities should be taken into account when selecting the most appropriate conversion therapy strategy.

In conclusion, anti-EGFR + CT represents an effective conversion therapy option for patients with initially unresectable mCRC, leading to higher RO resection rates and improved survival outcomes compared to CT alone. However, the increased risk of adverse events warrants careful patient selection and monitoring. Further research is needed to refine our understanding of the optimal use of targeted therapies in conversion therapy for mCRC, paving the way for personalized treatment strategies that maximize efficacy and minimize toxicity.

About this Article -

This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

This article is based on research published under:

DOI-LINK: 10.1093/annonc/mdy281.057, Alternate LINK

Title: Targeted Therapies In Conversion Therapy In Mcrc: A Systematic Review And Meta-Analysis

Subject: Oncology

Journal: Annals of Oncology

Publisher: Elsevier BV

Authors: B. Xing, B. Cui, Z. Gu, H. Peng

Published: 2018-10-01

Everything You Need To Know

1

What is conversion therapy, and why is it important in treating metastatic colorectal cancer (mCRC)?

Conversion therapy is a treatment approach used for initially unresectable metastatic colorectal cancer (mCRC). The aim is to shrink the tumor to a resectable state using systemic therapy, which often includes chemotherapy and targeted therapies like anti-EGFR and anti-VEGF antibodies. The significance lies in the potential to convert a non-curable situation into one where the tumor can be surgically removed (RO resection), improving survival rates.

2

What is the main difference in outcomes between using anti-EGFR versus anti-VEGF therapies in conversion therapy?

The primary difference lies in their impact on overall survival (OS). Patients receiving anti-EGFR therapies combined with chemotherapy (anti-EGFR + CT) experienced significantly longer OS compared to those treated with anti-VEGF therapies with chemotherapy (anti-VEGF + CT). Though both anti-EGFR and anti-VEGF offer benefits, the study highlights a potential survival advantage with anti-EGFR in the context of conversion therapy. It's crucial to note that this conclusion is based on a meta-analysis, and further research is needed.

3

What are anti-EGFR and anti-VEGF therapies?

Anti-EGFR and anti-VEGF are types of targeted therapies used in mCRC treatment. These therapies work by specifically targeting pathways that promote cancer growth and spread. Anti-EGFR antibodies block the epidermal growth factor receptor, while anti-VEGF antibodies target vascular endothelial growth factor, inhibiting the formation of new blood vessels that feed tumors. In conversion therapy, they are combined with chemotherapy (CT) to improve the chances of shrinking the tumor enough for surgical removal, also known as RO resection.

4

What does RO resection rate mean in the context of conversion therapy?

RO resection rate refers to the complete removal of the tumor during surgery. In the context of conversion therapy, the goal is to shrink the initially unresectable tumor to a size where RO resection becomes possible. The study showed that anti-EGFR + CT had a trend toward better RO resection rates compared to anti-VEGF + CT, although this difference was not statistically significant. Achieving RO resection is crucial because it represents a chance for improved survival outcomes.

5

Are there any safety concerns associated with using targeted therapies like anti-EGFR and anti-VEGF?

The study revealed that using anti-EGFR therapies with chemotherapy led to a higher incidence of adverse events compared to chemotherapy alone. This is a critical consideration because while targeted therapies like anti-EGFR and anti-VEGF can improve treatment outcomes, they can also cause side effects. Careful monitoring and management of side effects are essential to ensure patient safety and maintain a good quality of life during treatment. Balancing efficacy and safety is a key part of cancer treatment.

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