Efficacy of trastuzumab and trastuzumab adjunct chemotherapy HER2 amplified colorectal cancer: A systematic review and meta-analysis.

Abstract

e15596 Background: Colorectal Cancer (CRC) is a major global health burden, accounting for an estimated 10% of all tumour cases and reigning as the third most common cancer. Overexpression or amplification of human epidermal growth factor 2 ( HER2 ) is observed in nearly 3-6% of all CRC cases. Mounting evidence suggests that resistance to the anti-EGFR therapy, the standard for left-sided RAS/BRAFwt tumours, is associated with the presence of HER2 amplification. ERBB2 is a well-established oncogene and targeting HER2 has revolutionised therapy for breast and gastric cancers. Efforts targeting the same, through adjuvant trastuzumab therapy, in CRC have lagged although showing promising results in comparison to current treatment protocols. Our meta-analysis aims to clarify the improved survival rates and address the unmet needs of HER2-amplified CRC. Methods: A systematic search was conducted using PubMed, Google Scholar, and Scopus. A boolean expression was constructed to search the databases, and articles involving the administration of Trastuzumab therapy IN HER-2 amplified CRC were retrieved out of which studies reported Overall Response Rate (ORR) and adverse events. The statistical analysis was conducted in R-Studio. The outcomes analysed were the pooled proportion of ORR and proportions of grade 3 and higher adverse events to highlight the efficacy of Trastuzumab therapy in HER-2 amplified CRC. Random intercept logistic regression model was utilized. The I^2 Test evaluated the heterogeneity of the studies. Subgroup analysis was conducted based on different combination of drugs used in the treatment protocol. Results: A total of 12 studies involving 552 subjects were involved in the meta-analysis. The pooled proportion of the overall response ratio was estimated to be 0.428 [0.3317; 0.5142, 95% CI, I^2 = 69.9% p <0.001). The proportion of Grade 3 or higher adverse events was concerning with a pooled proportion of 0.424185 [0.2730; 0.5797, 95% CI, I^2 = 89.4% p <0.001]. The most effective chemotherapeutic combination was Trastuzumab and Lapatinib with an ORR of 0.80 (0.64;0.90) and the safest one was Pertuzumab and Trastuzumab with a pooled proportion of adverse events of 0.20 (0.12;0.32). Conclusions: The potential of HER2 as a target for cancer therapeutics remains far from fully realised, especially in CRC due to its lower incidence. Our study brings to light a significant improvement in survival rates of HER2-amplified advanced CRC with adjuvant trastuzumab therapy.These findings underscore the need for integration of HER2-targeted therapy into existing treatment protocols for appropriate cases to further improve patient outcomes.