Triplet chemotherapy combined with anti-EGFR treatment in RAS wild-type colon cancer: A network meta-analysis.

e15592 Background: The optimal first-line treatment for RAS wild-type (wt) metastatic colorectal cancer (mCRC) remains undetermined. Recently, several studies have explored the efficacy of first-line treatment regimens, including triplet chemotherapy (CT) combined with an anti-EGFR antibody, in comparison to either doublet CT combined with an anti-EGFR antibody, triplet CT combined with an anti-VEGF treatment, or triplet CT alone. However, none of these trials yielded conclusive results. Hence, we conducted a systematic review and an explorative network meta-analysis (NMA) of the available data. Methods: A systematic review was conducted, encompassing all phase II/III randomized clinical trials (RCTs) that compared a regimen consisting of triplet CT associated with an anti-EGFR treatment against different first-line systemic regimens for RAS-wt mCRC patients. Both pairwise and NMA were performed to establish direct and indirect comparisons of overall response rate (ORR) using a random effects model within the frequentist framework. Results: 7 RCTs (TRIPLETE, VOLFI, TRICE, PANIRINOX, AIO-CELIM2, FOCULM, DEEPER), involving a total of 1283 patients, were included in the analysis. Overall, 4 arms were identified, encompassing all possible combinations of CT, anti-EGFR treatment, and anti-VEGF treatment: arm A (triplet + anti-EGFR), arm B (doublet + anti-EGFR), arm C (triplet alone), and arm D (triplet + anti-VEGF). A benefit was demonstrated for all treatments associated with targeted therapy when compared to triplet alone; no difference was observed among groups A, B and D. Results of selected NMA comparisons are shown in the table 1. Additionally, we conducted a pairwise meta-analysis for ORR, which, due to available comparisons, was only feasible for groups A vs. B, A vs. C, and A vs. D; the results of this analysis confirmed the NMA findings (group A vs. group C, pooled OR: 4.23 (2.06 – 8.68)). Conclusions: Through indirect comparisons, no significant ORR benefit was found for triplet CT associated with anti-EGFR treatment compared to doublet CT combined with anti-EGFR treatment or triplet CT combined with anti-VEGF. All regimens incorporating targeted treatment demonstrated superior performance compared to triplet CT alone. Our findings do not advocate for the routine use of triplet CT associated with anti-EGFR treatment in this patient population; however, we await mature OS data from a few of the trials included in our analysis. Table: see text