Real-World Insights on Third-Line mCRC Treatment and Molecular Profiling in GI NETs

In recent discussions surrounding metastatic colorectal cancer (mCRC) and gastrointestinal neuroendocrine tumors (GI NETs), significant gaps in treatment efficacy and the evolving role of molecular profiling have been highlighted. Dr. Rocío García-Carbonero, a leading oncologist and researcher, presented critical findings from the PROMETCO study (NCT03935763) at the 2025 ESMO Gastrointestinal Cancers Congress, emphasizing the necessity of addressing the underrepresentation of patients with poorer performance statuses in clinical trials.

The PROMETCO study, a prospective observational analysis, enrolled 738 patients who had progressed on at least two prior lines of therapy. The study aimed to capture real-world data on treatment patterns, safety, and efficacy in a population often excluded from traditional clinical trials. Notably, approximately 10% of participants had an Eastern Cooperative Oncology Group (ECOG) performance status of 2, typically indicative of a higher disease burden and worse prognosis.

Dr. García-Carbonero reported an increase in adverse effects (AEs) among patients with poorer performance statuses, with a 10% higher incidence of AEs and serious AEs observed in this subgroup. The findings suggest a direct correlation between advanced disease characteristics, such as the presence of right-sided colon cancer and multiple metastatic sites, and the heightened risk of complications. “These insights are crucial for clinicians who manage these often-overlooked patient populations,” said Dr. García-Carbonero.

In a separate session, she discussed the management of poorly differentiated neuroendocrine carcinoma of the colon, a particularly aggressive subtype associated with a poor prognosis. The importance of molecular profiling was underscored, as approximately 20% of these tumors harbor druggable mutations. “Identifying these alterations can significantly enhance treatment options beyond standard chemotherapy,” Dr. García-Carbonero noted. For instance, she discussed a case where a BRAF mutation was identified, highlighting the need for clinicians to adopt a more molecularly driven approach in treating GI NETs.

The session also revealed a common misconception among clinicians regarding diagnostic imaging for neuroendocrine tumors. Despite gallium PET scans being suitable for well-differentiated tumors, many practitioners incorrectly considered them for poorly differentiated cases, indicating a need for improved education on the nuances of tumor differentiation.

As the field of oncology continues to evolve, the insights from the PROMETCO study and the discussions at the ESMO Congress reflect a pivotal shift towards a more comprehensive understanding of patient populations and the importance of individualized treatment plans. As molecular profiling becomes an integral part of clinical practice, future research will likely focus on developing targeted therapies that can further improve patient outcomes in mCRC and GI NETs.

The implications of these findings extend beyond clinical practice, as they emphasize the necessity for ongoing research to ensure that all patient demographics are represented in the development of treatment protocols. As Dr. García-Carbonero concluded, “It is essential to continue advancing our understanding of these complex malignancies to provide better care for all patients.”