Diabetes and Clinical Outcome in Patients With Metastatic Colorectal Cancer: CALGB 80405 (Alliance)

Abstract

Background Diabetes is a prognostic factor for some malignancies, but its association with outcome in patients with advanced or metastatic colorectal cancer (CRC) is less clear. Methods This cohort study was nested within a randomized trial of first-line chemotherapy and bevacizumab and/or cetuximab for advanced or metastatic CRC. Patients were enrolled at 508 community and academic centers throughout the National Clinical Trials Network. The primary exposure was physician-documented diabetes at the time of enrollment. The primary endpoint was overall survival (OS); secondary endpoints were progression-free survival (PFS) and adverse events. Tests of statistical significance were two-sided. Results Among 2326 patients, 378 (16.3%) had diabetes. The median follow-up time was 6.0 years. We observed 1973 OS events and 2173 PFS events. The median time to an OS event was 22.7 months among those with diabetes and 27.1 months among those without diabetes (HR = 1.27, 95% CI = 1.13 to 1.44; P < .001). The median time to a PFS event was 9.7 months among those with diabetes and 10.8 months among those without diabetes (HR = 1.16, 95% CI = 1.03 to 1.30; P = .02). Patients with diabetes were more likely to experience no less than grade 3 hypertension (8.1% vs 4.4%; P = .054) but were not more likely to experience other adverse events, including neuropathy. Conclusions Diabetes is associated with an increased risk of mortality and tumor progression in patients with advanced or metastatic CRC. Patients with diabetes tolerate first-line treatment with chemotherapy and monoclonal antibodies similarly to patients without diabetes.

The assessment of risk factors for long-term survival outcome in ypN0 patients with rectal cancer after neoadjuvant therapy and radical anterior resection

“…Diabetes mellitus is the only disease in which a direct impact on DFS was confirmed in locally advanced and disseminated colorectal cancer, regardless of systemic treatment. A direct interaction between diabetes and the progression of colorectal cancer is associated with hyperinsulinemia, an increase in insulin-like growth factor, hyperglycemia, and inflammation [ 30 ]. Comorbidities may result in the exclusion of patients from adjuvant therapy.…”

Body Mass Index and Weight Loss in Metastatic Colorectal Cancer in CALGB (Alliance)/SWOG 80405

“…Diabetes may reduce physiologic reserve or increase chemotherapy side effects such as peripheral neuropathy, prompting dose reduction or regimen change, consistent with prior studies reporting less aggressive CRC treatment in diabetic patients ( 60 , 61 ). A prior analysis of our study cohort demonstrated an association between diabetes and at least grade 3 hypertension, but no other adverse events ( 62 ). Diabetes was not associated with FOLFOX dose intensity.…”

The Assessment of Risk Factors for Long-term Survival Outcome in ypN0 Patients With Rectal Cancer After Neoadjuvant Therapy and Radical Anterior Resection

“…Diabetes mellitus is the only disease in which a direct impact on DFS was con rmed in locally advanced and disseminated colorectal cancer, regardless of systemic treatment. A direct interaction between diabetes and the progression of colorectal cancer is associated with hyperinsulinemia, an increase in insulin-like growth factor, hyperglycemia, and in ammation [25]. Comorbidities may result in the exclusion of patients from adjuvant therapy.…”