Post-induction Strategies in Metastatic Colorectal Cancer Patients Treated With First-Line Anti-EGFR-Based Treatment: A Systematic Review and Meta-Analysis

Few data from randomized clinical trials (RCTs) investigating the efficacy of post-induction strategies after the first-line treatment with anti-Epidermal Growth Factor Receptor (EGFR) in patients with metastatic colorectal cancer (mCRC) are available. A systematic review and metanalysis might therefore be useful to highlight and even strengthen these data. A literature search in Pubmed, Embase, American Society of Clinical Oncology (ASCO) Annual Meetings, ASCO Gastrointestinal Symposia, and European Society for Medical Oncology (ESMO) Congresses was performed. The search included RCTs of patients with mCRC treated with an initial period of cytotoxic chemotherapy (CT) in association with anti-EGFR (ie, panitumumab or cetuximab) as first-line regimen, and then switched to one of the following strategies: observation; maintenance with anti-EGFR, fluoropyrimidine (FP), or both; or continuing the induction regimen until disease progression or unacceptable toxicity. Outcomes of interest included overall survival (OS) and progression-free survival (PFS). The overall effect was pooled using the Mantel–Haenszel method fixed-effect model or the DerSimonian-Laird method random-effect model according to heterogeneity (I2). Analysis was performed on June 9, 2021. 7 studies (all phase II trials), including 1038 patients, were considered eligible for the meta-analysis. In all studies, CT (induction or maintenance with FP) + anti-EGFR until disease progression or unacceptable toxicity prolonged OS (HR = 0.72 [95%CI 0.61-0.86]; P < .01) and PFS (HR = 0.76, 95%CI 0.68-0.85; P < .01) compared to other agents (FP ± bevacizumab) or observation. Subgroup analyses for OS and PFS were performed according to type of maintenance therapy (containing or not containing single-agent anti-EGFR). Within patients evaluable for OS, CT + anti-EGFR combinations continued until disease progression were able to decrease the risk of death by 32% (HR 0.68; 95% CI 0.56-0.84; P < .01) and the risk of progression by 25% (HR 0.75; 95% CI 0.65-0.85; P < .01) over no maintenance or maintenance with anti-EGFR alone. Conversely, combination of CT + anti-EGFR were no better over anti-EGFR with FP in term of OS (HR = 0.81 [95%CI 0.60-1.09]; P = .17) and PFS (HR = 0.81 [95% 0.64, 1.01]; P = .06). Maintenance treatment with anti-EGFR + FP might be regarded as the better option following anti-EGFR based induction treatment in RAS wild-type mCRC, in terms of efficacy. This effect might be particularly amplified in left-sided BRAF wild-type mCRC patients. A higher level of evidence coming from phase III trials is auspicable.