Clinical News

Negative hyper-selection of patients with RAS wild-type metastatic colorectal cancer for panitumumab: A biomarker study of the phase III PARADIGM trial

2023-03-17 

Abstract: The phase III PARADIGM trial demonstrated that hyper-selected patients with no gene alterations would tend to be more beneficial with panitumumab than bevacizumab regardless of primary tumor sidedness.

Anti-EGFR monoclonal antibodies such as cetuximab and panitumumab played a crucial role in metastatic colorectal cancer (mCRC) treatment. Based on many published references, CRC patients with known KRAS (exon 2, 3, 4) or NRAS mutation (exon 2, 3, 4) would not benefit from anti-EGFR therapies. In addition, patients with BRAF V600E would not respond unless combined with a BRAF inhibitor. The phase III PARADIGM trial used the ctDNA-based NGS to investigate the relationship between biomarkers and panitumumab/bevacizumab-based treatment responses. The hyper-selected group was defined as no gene alterations, including PTEN, EGFR (extracellular domain), HER2 and MET amplification, ALK, RET, or NTRK1 fusions; while the gene-altered group was the opposite.

Patients without pre-defined genes detected (the hyper-selected group) was 79.2% in the left-sided tumor and 50% in the right-sided tumor. In the hyper-selected cohort, the outcome favored panitumumab with median overall survival (mOS) of 41.3 months compared with 34.4 months for bevacizumab. In the gene-altered group, the median OS was 19.0 vs 22.2 months for panitumumab and bevacizumab, respectively. 

In summary, ctDNA-based NGS can be used as a tool for selection, and patients with no gene alterations would tend to be more beneficial with panitumumab than bevacizumab regardless of primary tumor sidedness.
 

Negative hyperselection of patients with RAS wild-type metastatic colorectal cancer for panitumumab: A biomarker study of the phase III PARADIGM trial (Slide presentation in ASCO GI 2023)