Panitumumab Plus Intensified Chemo Underperforms in Liver-Limited mCRC Trial

In a significant advancement for metastatic colorectal cancer (mCRC) treatment, the phase 2 PANIRINOX-UCGI28 trial has revealed that the combination of panitumumab with intensified chemotherapy regimens, specifically FOLFIRINOX and modified FOLFOX6 (mFOLFOX6), failed to achieve meaningful clinical responses in patients with liver-limited, unresectable mCRC. This trial was presented at the 2025 ESMO Gastrointestinal Cancers Congress and marks a pivotal moment in understanding the efficacy of anti-EGFR therapies in this patient population.

The trial, which ran from October 2017 to August 2023, aimed to assess the effectiveness of these treatments in patients characterized by RAS/BRAF wild-type tumors. It enrolled 219 patients, all of whom had been deemed suitable for curative-intent therapy and had not previously received treatment, aside from fluoropyrimidine in the adjuvant setting. Notably, the trial utilized circulating tumor DNA (ctDNA) analysis for patient selection, a first in interventional studies involving anti-EGFR treatments.

Dr. Thibault Mazard, a medical oncologist at the Institut du Cancer de Montpellier Val d’Aurelle and lead investigator of the trial, stated, "Our findings indicate that the combination of intensified chemotherapy with panitumumab does not provide sufficient benefit for patients with liver-limited mCRC, leading us to reconsider its use in this context."

Among the participants receiving panitumumab plus FOLFIRINOX, the study found a complete response (CR) rate of 27.3% and an overall response rate (ORR) of 90.9%. Meanwhile, those treated with panitumumab plus mFOLFOX6 exhibited a CR rate of 23.5% and an ORR of 91.2%. Despite these figures, both treatment arms failed to meet the trial's primary endpoint of CR rate, and progression-free survival (PFS) and overall survival (OS) results were comparable across treatment groups, casting doubt on the effectiveness of the intensified chemotherapy approach.

The data indicated that common grade 3 or higher adverse effects varied between treatment arms, with diarrhea, peripheral neuropathy, and skin toxicities being the most frequently reported. Specifically, 34% of patients on the FOLFIRINOX regimen experienced diarrhea, compared to 12% in the mFOLFOX6 group.

Moreover, the ctDNA analysis presented a nuanced understanding of patient eligibility and treatment response. For the 216 patients analyzed, no significant correlation was found between mutation allele frequency and treatment efficacy, suggesting that while ctDNA analysis is crucial for patient selection, it may not influence treatment activity.

Dr. Linda H. M. Chen, Associate Professor of Oncology at Johns Hopkins University, emphasized the importance of these findings, stating, "The results of the PANIRINOX trial underscore the need for ongoing research to optimize treatment strategies for mCRC patients, particularly those with liver-limited disease. As we develop new therapies, understanding their limitations is just as vital as recognizing their strengths."

The implications of these findings are profound, particularly as the oncology community seeks to refine treatment protocols for mCRC. The results may alter clinical practices and guidelines in treating patients with liver-limited mCRC, reinforcing the significance of tailored therapeutic approaches based on individual patient profiles.

Looking ahead, while the PANIRINOX trial did not yield the anticipated results, it opens avenues for further research into alternative combinations and the role of ctDNA in guiding treatment decisions. As Dr. Mazard noted, "Our study highlights the complexities of mCRC treatment and the necessity for innovative strategies that can truly enhance patient outcomes in this challenging disease landscape."