Chemotherapy plus EGFR antibody as conversion treatment in RAS wild type, right-sided metastatic colon cancer: A systematic review and meta-analysis.

Abstract

e15568 Background: The optimal conversion strategy for right-sided RAS wild type (WT) metastatic colorectal cancer (mCRC) remains a contentious issue, especially regarding the role of EGFR antibodies. EGFR antibody treatment might be an attractive option in patients with contraindications to bevacizumab or in hyperselected patients with microsatellite stable subtypes and without RAS/BRAF/HER2 alterations, potentially allowing a shorter time to conversion surgery. Methods: We performed a systematic search of PubMed/MEDLINE and EMBASE for randomized trials reporting the overall response rate (ORR) and resection rate following chemotherapy (CT) plus anti-EGFR agents (cetuximab or panitumumab) for right-sided mCRC. Studies were selected regardless of whether the resection rate was a study endpoint or not. We used a random-effects model with generic inverse variance to compute pooled ORR and resection rates and to compare CT regimens combined with anti-EGFR or anti-VEGF agents. Results: Ten randomized trials with a total of 4465 mCRC patients were included; seven trials reported the resection rate as a secondary endpoint. 828/4465 (18.5%) patients were right-sided, of whom 419/828 (50.6%) patients received CT doublet or triplet plus anti-EGFR, 263/828 (31.8%) treated with CT plus bevacizumab, and 146/828 (17.6%) patients with CT alone. The ORR was significantly higher in the anti-EGFR group compared to CT alone (50.89% vs 31.03%, OR: 2.23 [95% CI: 1.50-3.32], p < 0.01). No significant difference in ORR was observed between the CT plus anti-EGFR and CT plus bevacizumab groups (50.89% vs 53.32%, OR: 0.89 [95% CI: 0.65-1.21], p = 0.44). Resection rates were 8.08% for CT plus anti-EGFR, 4.79% for CT plus bevacizumab, and 12.24% for CT alone, with no significant differences among the three arms (χ2= 2.15, p = 0.34). Subgroup analysis of RAS/BRAF WT patients with right-sided tumors from the PARADIGM and PEAK trials showed no difference in progression-free survival (PFS) between the CT plus anti-EGFR or bevacizumab groups (11.01m vs 11.60m, HR = 1.04 [95% CI: 0.58-1.50]), but there was a trend toward improved overall survival (OS) with anti-EGFR treatment (30.66m vs 28.67m, HR = 0.81 [95% CI: 0.45-1.17]). Conclusions: The data indicate that augmenting chemotherapy with anti-EGFR could be a viable conversion therapy for patients with RAS/BRAF WT right-sided mCRC, underscoring its potential utility in this subset of patients.