Cremolini C, et al. - In this phase 2 single-arm clinical trial, researchers prospectively examined the activity of cetuximab plus irinotecan as third-line treatment in patients with RAS and BRAF wild-type metastatic colorectal cancer who have acquired resistance to first-line irinotecan- and cetuximab-based therapy. Rechallenge with cetuximab plus irinotecan was noted to be active in 21% of patients with RAS and BRAF wild-type metastatic colorectal cancer. Benefits were noted only among those with RAS and BRAF wild-type circulating tumor DNA at the time of rechallenge as per preplanned circulating tumor DNA profiling. This suggests a possible utility of evaluating RAS mutational status on circulating tumor DNA (ctDNA) in selecting candidate patients.