Switch from cetuximab to panitumumab during encorafenib-based therapy in BRAF V600E mutated metastatic colorectal cancer: An international multicenter analysis from the AGEO group

BRAF V600E mutation (BRAFm) is present in around 8 % of metastatic colorectal cancers (mCRC) and is associated with a poor prognosis. The encorafenib-cetuximab combination (ENCO-CET) is currently the standard second-line treatment of BRAFm mCRC. However, 2–5 % of patients treated with cetuximab experience grade 3–4 infusion-related reactions (IRRs), leading to treatment discontinuation. In addition, BRAF inhibitors must be combined with an anti-EGFR to have any efficacy in BRAFm mCRC. As panitumumab (PANI) is associated with a lower risk of IRRs, this study aimed to assess the safety and efficacy of ENCO-PANI as an alternative strategy in patients experiencing an IRR to CET. We retrospectively collected BRAFm mCRC patients that switched ENCO-CET for ENCO-PANI following an IRR to CET. Twenty pts were identified across 12 centers from 4 countries. Most were male (12/20), 11/20 had right-sided primary tumor and 5/20 pts were dMMR/MSI. Median age was 66, treatment line was 2nd line in 85 % and 3rd line in 15 % of patients; 19 patients started ENCO-CET and switched to ENCO-PANI (cycle 2 or 3) and 1 received ENCO-PANI upfront due to patient's choice. Response rate was 25 % and disease control rate 85 %. Median progression-free survival was 6.2 and median overall survival 11 months. Adverse events (AEs) during ENCO-PANI occurred in 15/20, mostly G1-G2. No new IRRs nor toxic deaths were reported. ENCO-PANI appears to be as safe and effective in pts treated for a BRAFm mCRC unable to continue CET and may represent a valid alternative therapeutic option in this setting.