432P Toxicity and efficacy of 1st line cetuximab (cetux)-based therapy in RAS wildtype (WT) older patients (pts) with metastatic colorectal cancer (mCRC): A pooled analysis from 1,274 pts in the ARCAD database

Background With a median age at diagnosis of around 70 years (yrs), CRC is a disease that affects many older adults. We investigated the toxicity and efficacy of adding cetux to doublet chemotherapy (DC) in older pts. Methods RAS WT pts receiving 1st line DC + cetux (n = 932) or DC (n = 342) from 6 mCRC trials in the ARCAD database were included. Toxicity was measured by adverse events (AE) with CTCAE grade ≥ 3 (G3+) and compared by age group (≥ 70 vs < 70 yrs). OS and PFS between DC +/- cetux in 3 randomized trials were compared using stratified Cox model, adjusting for covariates. Interaction between age and treatment groups was tested. Associations between age groups for DC + cetuximab in all 6 trials were evaluated for outcomes and toxicity by multivariable cox model and logistic regression. Results RAS WT pts ≥ 70 yrs (age median [range] 73 [70-89], 70% male) were more likely than pts < 70 (age median [range] 58 [19-69], 63% male) to have PS 1 (50% vs 42%; p = 0.048), right colon (42% vs 29%; p = 0.013), and lung metastasis (40% vs 30%; p = 0.005). Pts ≥ 70 (vs < 70) had no difference in G3+ AE for neutropenia/leukopenia (23% vs 22%; p = 0.84), diarrhea (14% vs 12%; p = 0.83) or nausea/vomiting (9% vs 8%; p = 0.87). When comparing DC +/- cetux, no significant difference in OS was observed within each age group. PFS improved by adding cetux in pts < 70. Interaction tests were not significant. Pts ≥ 70 (vs < 70) receiving DC + cetux had similar PFS (HRadj [95% CI] = 1.23 [0.99 – 1.5]; p = 0.063) but inferior OS (HRadj [95% CI] = 1.38 [1.1 – 1.7]; p = 0.006).