Experts Highlight Notable Advances in Colorectal Cancer at 2025 ESMO

Dr. Joshua Sabari, an assistant professor in the Department of Medicine at NYU Grossman School of Medicine and director of High Reliability Organization Initiatives at Perlmutter Cancer Center, sat down to interview Dr. Michael Cecchini following the 2025 European Society for Medical Oncology (ESMO) Congress. He discussed advances in colorectal cancer management and key data presented at the meeting.

Cecchini is an associate professor of medicine (medical oncology), co-director of the Colorectal Program within the Center for Gastrointestinal Cancers, medical oncology section lead for the National Accreditation Program for Rectal Cancer, phase 1 investigator at Yale Cancer Center, and director of the GI Clinical Research Team at the Yale Center for Gastrointestinal Cancers.

The interview began with an overview of the current approach to treating metastatic colorectal cancer. Cecchini emphasized that the initial evaluation focuses on determining whether patients have a potentially curative pathway through surgery combined with chemotherapy. Standard first-line regimens include FOLFOX or FOLFIRI, both of which combine fluorouracil (5-FU) with other agents such as oxaliplatin or irinotecan. Targeted therapies such as Avastin (bevacizumab), which inhibits vascular endothelial growth factor (VEGF), or Erbitux (cetuximab) and Vectibix (panitumumab), which target epidermal growth factor receptor (EGFR), may be incorporated based on tumor characteristics.

Cecchini presented new third-line data evaluating telisotuzumab adizutecan (Temab-A; ABBV-400) an antibody-drug conjugate (ADC) directed at c-MET, in combination with Avastin. This ADC delivers a topoisomerase I inhibitor payload to cancer cells expressing c-MET, a protein often upregulated in advanced or treatment-resistant tumors. In a randomized study of 66 patients with heavily pretreated colorectal cancer, no responses were observed in the standard-of-care arm, whereas the investigational arms achieved response rates of 19% and 30% at two different telisotuzumab adizutecan dosing levels, respectively.

The combination also demonstrated improved progression-free and overall survival compared with current therapies, suggesting a potential treatment option that may not require preselection for c-MET expression.

Cecchini also highlighted new data from the DYNAMIC study evaluating circulating tumor DNA (ctDNA)-guided therapy in stage 3 colorectal cancer. Although previous studies suggested utility for ctDNA in stage 2 disease, escalation or de-escalation of treatment based on ctDNA status in stage 3 disease did not improve outcomes and may have negatively impacted certain patients. He concluded that ctDNA testing remains investigational for this population. Sabari agreed, noting the potential of ctDNA and related biomarkers for future clinical decision-making as technologies and therapeutics continue to evolve.

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