Targeted Therapy and Immunotherapy in Elderly Patients with Metastatic Colorectal Cancer

At initial diagnosis, over half of the patients with metastatic colorectal cancer (mCRC) are aged 65 years or older. In this population, age-related declines in organ reserve and the presence of comorbidities can significantly weaken drug tolerance and affect treatment outcomes. However, existing clinical guidelines, largely based on clinical trials involving younger, fitter adults, may not be fully applicable to older patients, particularly those are vulnerable. Moreover, chronologic age and commonly used performance assessment tools, such as the Eastern Cooperative Oncology Group and Karnofsky Performance Status scores, are insufficient for accurate evaluation of physiological fitness in older adults. To provide evidence-based references for clinicians, this review summarizes advances in targeted therapy and immunotherapy for elderly patients with mCRC over the past five years, with a focus on vascular endothelial growth factor (VEGF) targeting agents, epidermal growth factor receptor (EGFR) inhibitors, multi-targeted tyrosine kinase inhibitors (TKIs) and single-agent immunotherapy. Overall, for elderly patients assessed as fit, first-line treatment may include dose-reduced doublet chemotherapy combined with VEGF targeting agents, or alternatively, single-agent chemotherapy plus VEGF targeting agents. For vulnerable elderly patients with mCRC, single-agent chemotherapy with VEGF targeting agents remains the preferred first-line strategy, while RAS wild-type left-sided tumors may benefit from single-agent chemotherapy plus EGFR inhibitors. Although multi-targeted TKIs have shown positive outcomes in elderly patients who are intolerant to other therapies. There is currently no evidence supporting their use in first-line treatment or combination therapy. In terms of immunotherapy, similar to the general mCRC population, single-agent immunotherapy is recommended as a first-line option for elderly microsatellite instability-high/mismatch repair-deficient patients. Notably, integrating comprehensive geriatric assessment into clinical practice can facilitate personalized treatment strategies, particularly for vulnerable and frail patients.