Data from Genomic Characterization and Clinical Outcomes of Patients with Peritoneal Metastases from the AACR GENIE Biopharma Collaborative Colorectal Cancer Registry

Abstract

<div>Abstract<p>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 American Association of Cancer Research 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 drug regimen were estimated and adjusted for the left truncation bias. A total of 1,281 patients were analyzed, 244 (19%) had PM at time of advanced disease. PM were associated with female sex [OR: 1.67; 95% confidence interval (CI): 1.11–2.54; <i>P</i> = 0.014] and higher histologic grade (OR: 1.72; 95% CI: 1.08–2.71; <i>P</i> = 0.022), while rectal primary tumors were less frequent in patients with PM (OR: 0.51; 95% CI: 0.29–0.88; <i>P</i> < 0.001). <i>APC</i> occurred less frequently in patients with PM (<i>N</i> = 151, 64% vs. <i>N</i> = 788, 79%) while <i>MED12</i> alterations occurred more frequently in patients with PM (<i>N</i> = 20, 10% vs. <i>N</i> = 32, 4%); differences in <i>MED12</i> were not significant when restricting to oncogenic and likely oncogenic variants according to OncoKB. Patients with PM had worse OS (HR: 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 <i>MED12</i> and <i>APC</i> alterations were identified between patients with and without PM. PM were associated with shorter OS but not with PFS from first-line treatment.</p>Significance:<p>Utilizing the GENIE BPC registry, this study found that PM in patients with colorectal cancer occur more frequently in females and right-sided primary tumors and are associated with worse OS. In addition, we found a lower frequency of <i>APC</i> alterations and a higher frequency in <i>MED12</i> alterations in patients with PM.</p></div>