The PARADIGM trial, a significant study in the field of metastatic colorectal cancer (mCRC) treatment, has provided new insights into the effectiveness of EGFR-targeting therapy. This trial specifically targeted patients with newly diagnosed mCRC who had RAS wild-type tumors. Participants were randomized to receive first-line chemotherapy with FOLFOX (folinic acid, fluorouracil, and oxaliplatin) plus either bevacizumab or panitumumab, with the primary endpoint being overall survival.
A notable aspect of the trial was its focus on the sidedness of tumors as a strong biomarker, leading to an amendment in the protocol to include only left-sided tumors. Out of approximately 800 enrolled patients, about 600 had left-sided tumors. The study adopted a hierarchical approach, first evaluating the left-sided tumors and, if positive, then assessing the entire study population.
The results were promising, with the panitumumab arm showing an improvement in overall survival over the bevacizumab arm, evidenced by a hazard ratio of about 0.7. This improvement translated to an increase in survival from 34 months to around 38 months. Similar positive outcomes were observed across the whole cohort, reinforcing the validity of previous phase 3 trial analyses. These findings suggest that patients with RAS wild-type, left-sided tumors should be considered for EGFR monoclonal antibody therapy, particularly if they are also BRAF wild type and do not have HER2-amplified tumors.
Despite the progression-free survival being fairly equivalent between the two arms, the panitumumab arm demonstrated a higher response rate and increased rates of curative resection. This data underscores the importance of considering EGFR-targeting therapy in the treatment strategy for eligible mCRC patients, marking a significant step forward in personalized cancer treatment.
