Supplementary Material for: REAL-WORLD OUTCOMES OF ANTI-EGFR RECHALLENGE GUIDED BY LIQUID BIOPSY IN METASTATIC COLORECTAL CANCER

INTRODUCTION: In patients with metastatic colorectal cancer (mCRC) without RAS/BRAF somatic variants, first-line anti-EGFR antibodies plus chemotherapy improve survival. Retreatment of responders with anti-EGFR rechallenge accumulates less evidence for benefit when compared with other available third-line treatments. MATERIAL AND METHODS: A unicentric retrospective cohort of patients with somatic RAS/BRAF wild type (wt) mCRC, treated with irinotecan/cetuximab within the definition of rechallenge, was selected between 2018 and 2023. Liquid biopsy for confirmation of RAS/BRAF status was required previously to rechallenge. Outcomes measured were disease control and overall response rate (ORR) at first response evaluation, overall survival (OS) and progression-free survival (PFS). Toxicities were reported and graded according to Common Terminology Criteria for Adverse Events. RESULTS: Sixteen patients received irinotecan/cetuximab rechallenge, with a median follow-up of 12.8 months (2.6-46.5). Eighty one percent were male with a median age of 63 years (51-84). Rechallenge was prescribed as third-line therapy in 88%. Overall, 31% achieved partial response and 56% disease control. Median PFS for rechallenge was 5.3 months (IC95% 3.3-7.4) and median OS was 12.7 months (IC95% 8.3-17.1). Sixty-two adverse events were reported, 11% grade 3, none leading to discontinuation of treatment. Seventy-five percent of the patients had acneiform rash of any grade. In subgroup analysis, development of grade ≥2 rash (n=9) correlated with superior PFS than grade 1 or absence of rash [HR 0.30 (IC95% 0.1-1.0), p=0.05]. DISCUSSION: Despite the absence of randomized phase III trials comparing rechallenge and other available therapies for third-line treatment of RAS/BRAF wt mCRC, cumulating evidence allows for the use of anti-EGFR rechallenge in patients selected by liquid biopsy that may benefit from disease response. Skin toxicity emerges as a potential biomarker for response in anti-EGFR rechallenge. CONCLUSIONS: In our cohort, in accordance with previous studies, anti-EGFR rechallenge in liquid biopsy confirmed RAS/BRAF wt mCRC showed clinically relevant response rates and disease-free survival, in third line treatment and beyond.