Colorectal Cancer

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•	Nivolumab plus ipilimumab continued to show clinically meaningful PFS improvement over nivolumab alone in MSI-H/dMMR mCRC.
Nivolumab/Ipilimumab Maintain PFS Benefit vs Nivolumab Monotherapy in MSI-H/dMMR CRC

October 20th 2025

With a median follow-up of 50.1 months, nivolumab plus ipilimumab achieved a median PFS of not reached compared with 60.8 months with nivolumab monotherapy in this CRC population.

Data from the STELLAR-303 trial support zanzalintinib plus atezolizumab as a potential chemotherapy-free option in previously treated metastatic CRC.
Zanzalintinib Combo Improves Survival in Pretreated Metastatic CRC

October 20th 2025

Findings from the DeFianCe trial support further development of sirexatamab in DKK1-high previously treated metastatic colorectal cancer.
Sirexatamab Combo Shows Efficacy in DKK1-High Metastatic CRC Subgroups

October 19th 2025

Data from the INTERCEPT study support ctDNA clearance as a useful end point for potential benefit in studies assessing novel therapeutics.
Adjuvant Therapy Confers Postoperative ctDNA Clearance, DFS Benefit in CRC

October 19th 2025

Investigators are actively enrolling patients with locally advanced rectal cancer in the phase 1b FORTRESS trial evaluating NG-350A plus chemotherapy.
FDA Grants Fast Track Designation to NG-350A for pMMR Rectal Cancer

October 15th 2025

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Targeted Therapy in Rectal Cancer

August 1st 2007

Epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) are often overexpressed in colorectal cancer and are associated with inferior outcomes. Based on successful randomized phase III trials, anti-EGFR and anti-VEGF therapeutics have entered clinical practice. Cetuximab (Erbitux), an EGFR-specific antibody, is currently approved in the United States in combination with irinotecan (Camptosar) for patients with metastatic colorectal cancer refractory to irinotecan or as a single agent for patients unable to tolerate irinotecan-based therapy. In retrospective analyses, patients with EGFR-expressing rectal cancer undergoing neoadjuvant radiation therapy had a significantly inferior disease-free survival and lower rates of achieving pathologic complete response. Based on the positive data in metastatic colorectal cancer and synergy with radiation therapy seen in preclinical models, there is a strong rationale to combine cetuximab with neoadjuvant radiation therapy and chemotherapy in rectal cancer. Bevacizumab (Avastin), a VEGF-specific antibody, was the first antiangiogenic agent to be approved in the United States for use in combination with standard chemotherapy in the first- and second-line of treatment in metastatic colorectal cancer. VEGF-targeted therapy may lead to indirect killing of cancer cells by damaging tumor blood vessels, and may increase the radiosensitivity of tumor-associated endothelial cells. VEGF blockade can also "normalize" tumor vasculature, thereby leading to greater tumor oxygenation and drug penetration. This review will address completed and ongoing trials that have established and continue to clarify the effects of these agents in rectal cancer.