HER2 expression and genOmic characterization of rESected brain metastases from colorectal cancer: the HEROES study

Background: Little is known about prognostic factors of brain metastases (BM) from colorectal cancer (CRC). HER2 amplification/overexpression (HER2+) was previously described; its impact on prognosis remains uncertain. Methods: In the translational study HEROES, extensive molecular analysis was performed on primary CRC (prCRC) and their matched resected BM by means of NGS comprehensive genomic profiling and HER2 status as assessed by immunohistochemical/ in situ hybridization. Count of tumour-infiltrating lymphocytes (TILs) was also performed. Primary objective: to describe the molecular landscape of paired BM/prCRC. Secondary objectives: to search for new prognostic biomarkers of outcome after BM resection: intracranial-only Progression-Free Survival (BM-iPFS), Progression-Free Survival (BM-PFS), and Overall Survival (BM-OS). Results: Out of 22 patients having paired samples of prCRC and BM, HER2+ was found on 4 (18%) BM, 3 (75%) of which also HER2+ in matched prCRC. Lower tumour mutation burden (HR 3.08; 95%CI 1.06-8.93; p = 0.0386) and HER2-negative BM (HER2neg) (HR 7.75;95%CI 1.97-30.40; p = 0.0033) were associated with longer BM-iPFS; HER2neg BM (HR 3.44; 95%CI 1.03-11.53; p = 0.0449) and KRASmut BM (HR 0.31; 95%CI 0.12-0.80; p = 0.0153) conferred longer BM-PFS. Longer BM-OS was found in pts with TILs-enriched (≥1.6/HPF) BM (HR 0.11; 95%CI0.01-0.91; p = 0.0403). Conclusions: This study shows HER2+ enrichment in both BM and their prCRC. TILs-enriched BM conferred better BM-OS.