NSABP FC‐6: Surgical conversion rate in colorectal cancer patients with unresectable, KRAS wild‐type liver metastases receiving mFOLFOX7 plus cetuximab

• Published in: Journal of surgical oncology Vol. 126; no. 8; pp. 1494 - 1503
• Main Authors: Wagman, Lawrence D., Geller, David A., Jacobs, Samuel A., Petrelli, Nicholas J., Allegra, Carmen J., Lipchik, Corey, Pogue‐Geile, Katherine L., Srinivasan, Ashok, Wang, Ying, O'Connell, Michael J.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc 01.12.2022
• Subjects: Chemotherapy; Colorectal cancer; CRC subtypes; HTG‐Edge gene expression; metastatic colorectal cancer; Monoclonal antibodies; Targeted cancer therapy
• ISSN: 0022-4790; 1096-9098
• DOI: 10.1002/jso.27078

Purpose This study sought to determine the R0 resection rate in KRAS wild‐type (WT), liver‐only metastatic colorectal cancer (CRC) patients initially identified as having unresectable disease who were treated with FOLFOX7 plus cetuximab. Exploratory molecular analyses were undertaken before and after treatment. Methods Twenty patients were enrolled. None had prior adjuvant chemotherapy. Cetuximab was added to a FOLFOX7 backbone and administered at 500 mg/m2 every 14 days with dose reductions to 400 and 300 mg/m2 in the event of toxicity. In the absence of toxicity, dose‐escalations to 600, 700, and 800 mg/m2 were allowed. The mean dose of cetuximab (mg/m2/week) throughout the study was 289 mg/m2. Paired samples were collected for correlative studies, where feasible. Results We assessed the conversion rates from unresectable to resectable in hepatic‐only, KRAS exon 2 WT mCRC. Seventeen of 20 patients undergoing chemotherapy were considered resectable by imaging criteria; R0 resection was achieved in 15/20 patients. Molecular profiling revealed heterogeneity between patients at the gene‐expression, pathway signaling, and immune‐profile levels. Conclusions Although 15/20 (75%) converted to R0 resection, by 2 years, 10/15 R0 resections had recurred. Therefore, chemotherapy plus cetuximab is of limited long‐term benefit in this setting. ctDNA analysis may guide additional therapy including immunotherapy.