Systemic Chemotherapy for Metastatic Colitis-Associated Cancer Has a Worse Outcome Than Sporadic Colorectal Cancer: Matched Case Cohort Analysis

We studied outcome, defined as response rate, progression-free, and overall survival (OS), in a cohort of 18 stage IV colitis-associated bowel cancer (CAC) patients compared to 18 matched controls with sporadic bowel cancer receiving the same standard chemotherapy regimens. Analysis of genomic alterations was performed on all tumor specimens. Although responses rates were similar, response durations and OS were significantly worse for the CAC cohort. Newer therapies are needed to treat CAC. Background: Colitis-associated cancers (CAC) are a catastrophic complication of inflammatory bowel disease; at diagnosis, CAC is frequently at an advanced stage. Although the genomic alterations (GA) in CAC are different from sporadic colorectal cancer (CRC), the same systemic therapies are used. We compared clinically relevant outcomes using standard care systemic chemotherapy of stage IV CAC versus a matched patient control cohort of stage IV CRC patients. Patients and Methods: A retrospective matched cohort design was used. Eighteen cases of stage IV CAC (7 ulcerative colitis, 11 Crohn disease) and 18 CRC were identified. GA analysis was available for all patients. Outcome endpoints included response rate and response duration, progression-free survival, and OS. Results: Although the response rates were similar (CAC 35.7% vs. CRC 57.1%, P=.45), the median duration of response for CAC was significantly shorter (1.4 months, vs. CRC 11.8 months, P=.006). There was no difference in dose density of first-line therapy between cohorts, suggesting that shorter response duration was due to more rapid development of chemotherapy resistance. Median OS was significantly shorter for CAC patients (13 vs. 27.6 months, P=.034). As expected, there was a difference in the spectrum of GA between CAC and CRC cohorts. However, GA associated with poor prognosis (eg, B-Raf) were no more frequent in the CAC cohort. Conclusion: Clinically meaningful outcomes of duration of response and OS are worse for CAC versus sporadic CRC patients treated with FOLFOX or FOLFIRI as first therapy for metastatic disease. (C) 2020 Elsevier Inc. All rights reserved.