Genomic characterization and clinical outcomes of patients with peritoneal metastases from the AACR GENIE Biopharma Collaborative colorectal cancer registry.

Peritoneal metastases (PM) are common in metastatic colorectal cancer (mCRC). We aimed to characterize patients with mCRC and PM from a clinical and molecular perspective using the AACR Genomics Evidence Neoplasia Information Exchange (GENIE) Biopharma Collaborative (BPC) registry. Patients' tumor samples underwent targeted next generation sequencing. Clinical characteristics and treatment outcomes were collected retrospectively. Overall survival (OS) from advanced disease and progression-free survival (PFS) from start of cancer-directed regimen were estimated and adjusted for left truncation bias. A total of 1281 patients were analyzed, 244 (19%) had PM at time of advanced disease. PM were associated with female sex (odds ratio (OR) 1.67, 95% confidence interval (CI) 1.11-2.54; p=0.014) and higher histological grade (OR 1.72, 95%CI 1.08-2.71, p=0.022), while rectal tumors were less frequent in patients with PM (OR 0.51, 95%CI 0.29-0.88, p<0.001). APC occurred less frequently in patients with PM (N=151, 64% vs. N=788, 79%) while MED12 alterations occurred more frequently in patients with PM (N=20,10% vs. N=32,4%); differences in MED12 were not significant when restricting to oncogenic and likely oncogenic variants according to OncoKB. Patients with PM had worse OS (hazard ratio 1.45, 95%CI 1.16-1.81) after adjustment for independently significant clinical and genomic predictors. PFS from initiation of first-line treatment did not differ by presence of PM. In conclusion, PM were more frequent in females and right-sided primary tumors. Differences in frequencies of MED12 and APC alterations were identified between patients with and without PM. PM were associated with shorter OS but not with PFS from first-line treatment.