Efficacy of combination therapy with anti-EGFR antibody as first-line treatment for RAS wild-type metastatic colorectal cancer according to anatomical tumor location from the Analysis and Research in Cancers of the Digestive System (ARCAD) database.

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146 Background: The combination of anti-EGFR antibody plus doublet chemotherapy has become the standard first-line treatment for RAS wild-type (wt), left-sided metastatic colorectal cancer (mCRC), but its efficacy in each anatomical tumor location remains unclear. Methods: To evaluate the efficacy of anti-EGFR antibody combination therapy compared with bevacizumab combination therapy, from 48,326 Individual patient (pt) data from 72 studies in ARCAD mCRC database, 2,867 pts with RAS wt mCRC who received doublet chemotherapy plus either anti-EGFR antibody or bevacizumab as first-line treatment were selected from 12 randomized studies (FIRE-3, CALGB80495, CRYSTAL, PRIME, CAIRO2, OPUS, TRIBE, TRIBE2, ATOM, CCOG1201,TRICOLORE, and PARADIGM). Primary objective was overall survival (OS), and secondary objectives were progression-free survival (PFS) and overall response rate (ORR); Hazard ratio (HR) and Odds ratio (OR) were adjusted for ECOG-PS, age, and gender. Results: Anti-EGFR antibody and bevacizumab were administrated in 1,451 and 1,416 pts, respectively. Baseline characteristics were as follows (anti-EGFR antibody/bevacizumab): median age, 63.0/63.0 years female, 35.8/35.2%; ECOG-PS 0, 63.7/68.4%; and right-sided tumor (cecum, ascending, and transverse colon), 402/413. Adding anti-EGFR antibody to doublet chemotherapy significantly improved OS and ORR in left-sided tumor compared to adding bevacizumab, but did not improve efficacy in right-sided tumor (Table). Analysis of anatomical tumor location revealed a tendency toward improved efficacy of anti-EGFR antibody combination therapy toward the distal side, but this trend was not clear in the ascending, transverse, and descending colon. Conclusions: Tumor-sidedness is an important indicator when selecting anti-EGFR antibody therapy, but anatomical tumor location may also need to be considered. N(Anti-EGFR/ bevacizumab) OSHR (95% CI) PFSHR (95% CI) ORROR (95% CI) Right-sided 402/413 1.09 (0.94-1.27)p=0.2683 1.14 (0.99-1.32)p=0.0707 1.09 (0.82-1.47)p=0.5494 Left-sided 1,049/1,003 0.86 (0.78-0.95)p=0.0040 0.95 (0.87-1.04)p=0.2991 1.66 (1.36-2.03)p<0.0001 Cecum 42/55 1.27 (0.83-1.95)p=0.2735 1.10 (0.71-1.71)p=0.6737 1.01 (0.46-2.61)p=0.8264 Ascending 67/80 0.93 (0.64-1.34)p=0.6837 1.30 (0.93-1.82)p=0.1257 1.26 (0.60-2.65)p=0.5350 Transverse 83/77 0.97 (0.67-1.40)p=0.8758 1.02 (0.73-1.43)p=0.9197 0.82 (0.42-1.59)p=0.5553 Descending 45/35 1.10 (0.65-1.85)p=0.9684 1.09 (0.67-1.78)p=0.7244 0.97 (0.32-3.00)p=0.9625 Sigmoid 239/244 0.85 (0.69-1.04)p=0.1177 1.00 (0.83-1.22)p=0.9836 2.46 (1.58-3.84)p<0.0001 Rectum 211/313 0.80 (0.65-0.97)p=0.0256 0.88 (0.73-1.06)p=0.1639 1.49 (0.99-2.22)p=0.0533