Brain metastasis in patients with primary gastrointestinal malignancy on anti-HER2 therapy.

e16067 Background: The incidence of brain metastasis in gastrointestinal (GI) malignancies is rare, estimated at less than 1%. However, its occurrence is associated with devastating outcomes. With the advent and prolonged use of Anti-HER2 therapy in patients expressing HER2 in their primary malignancy, there appears to be an increasing trend in brain metastasis, though the reason is unknown. Methods: This study included patients with a confirmed diagnosis of primary GI cancer treated at MD Anderson Cancer Center between 2000 and 2024. Data was extracted from electronic health records (EHR) and the tumor registry using the Palantir Foundry platform (Palantir Technologies, Denver, CO). Patients were included if their primary malignancy exhibited positive HER2 expression (IHC 3+) or ERBB2 amplification. The cohort was divided into two groups based on treatment received: (1) those who received Anti-HER2 therapy and (2) those who did not receive Anti-HER2 therapy. The Institutional Review Board (IRB) of MD Anderson Cancer Center approved the study. Results: Out of 83,329 patients with gastrointestinal cancers, HER2 testing was performed on 13,153 individuals, identifying HER2 positivity or ERBB2 amplification in 571 patients: 49% with gastroesophageal cancer, 37% with colorectal cancer, 11.5% with Biliary tract cancers, 1% with appendiceal cancer, 0.8% with small intestinal cancer, and 0.7% with anal cancer The cohort of 571 patients comprised 68% males (387 patients) and 32% females (184 patients), with a median age at diagnosis of 58 years (range 21–89 years).Among the 177 patients receiving anti-HER2 therapy, (trastuzumab and pertuzumab or trastuzumab deruxtecan) 33 (18%) developed brain metastasis, while 20 (5%) of the 396 patients not receiving anti-HER2 therapy developed brain metastasis, p < 0.001 (RR = 3.7). Of the 33 patients with brain metastases in the anti-HER2 therapy group, 31 (94%) had metastases to other sites, while among the 20 patients with brain metastases in the non-anti-HER2 therapy group, 15 (75%) had metastases to other sites, p = 0.08. The median time between disease diagnosis and the development of brain metastases was 19 months for the group receiving anti-HER2 therapy and 13 months for the group not receiving anti-HER2 therapy, with a statistically non-significant p-value of 0.7. The median duration from the start of anti-HER2 therapy to the development of brain metastasis was 14 months (range 1 to 86). Conclusions: These findings suggest a significantly higher incidence of brain metastasis in patients treated with anti-HER2 therapy (18%) compared to those who did not receive this treatment (5%). These findings underscore the need for further research to understand the mechanisms driving this trend and to explore strategies for early detection and prevention of brain metastasis in this population.