Circulating tumor DNA to guide rechallenge with panitumumab in metastatic colorectal cancer

Despite advances in molecular segmentation of metastatic colorectal cancer, beyond RAS status therapeutic actionability remains confined to limited subgroups. Optimization of available treatments is warranted. Rechallenge with anti-EGFR monoclonal antibodies is often empirically used with some benefit as late-line therapy. Previous studies found that mutant RAS and EGFR ectodomain clones, which emerge in blood during EGFR blockade, decline upon antibody withdrawal, leading to regain of drug sensitivity. The phase 2 CHRONOS trial, at four centers in Italy, found that liquid biopsy-driven rechallenge with panitumumab resulted in further objective responses in 30% of patients with RAS/BRAF wild-type mCRC having first achieved objective respons and then progression in any treatment line with an anti-EGFR antibody containing regimen. Disease control was seen in 63% of patients. The authors conclude that these results compare favorably with standard third-line treatments.