Anti-Human Epidermal Growth Factor Receptor 2 therapies in metastatic colorectal cancer: a systematic review and meta-analysis

BACKGROUND: HER2 amplification identifies a subgroup of colorectal cancer with poorer prognosis and resistance to anti-EGFR therapy. We conducted a systematic review and a meta-analysis of available data on anti-HER2 treatments (HER2Tx) in mCRC patients (pts). METHODS: A systematic literature search was performed, encompassing phase II/III clinical trials (CTs) investigating HER2Tx in HER2-overexpressed mCRC. CTs reporting HER2Tx plus chemotherapy were excluded. Primary endpoints were objective response rate (ORR) and disease control rate (DCR). Fixed and random-effect models were applied according to heterogeneity assessed through I 2 statistics. Progression-free survival (PFS) and overall survival (OS) were compared descriptively and pooled using the weighted median of medians (WM) with approximated 95% CIs. Subgroup analyses by HER2Tx were carried out. RESULTS: The analysis included 10 CTs evaluating Trastuzumab-Pertuzumab (T + P, 5 CTs,), Trastuzumab Deruxtecan (T-DXd, 2 CTs), Trastuzumab-Lapatinib (T + L, 1 CT), Pertuzumab-TDM1 (P+TDM1, 1 CT), and Trastuzumab-Tucatinib (T-Tu, 1 CT), for a total of 467 pts. The pooled ORR was 33.7% (29.6%-38.1%), and the pooled DCR was 68.5% (58.1%-77.4%). The WM OS was 13.4 months (10-24.1) and WM PFS was 5.5 months (4.1-6.9). The T-DX and T-Tu groups showed higher ORR and DCR (38% and 39% respectively, 85.1% and 73.2% respectively) compared to the T + P group (ORR, 30%; DCR, 52.6%). CONCLUSIONS: HER2Tx demonstrated efficacy in pretreated CRC pts, exhibiting good DCR and ORR alongside promising PFS and OS. T-DXd and T-Tu appear to outperform T + P; however, further studies are needed.