Survival and hemoglobin A1c in metastatic castrate resistant prostate cancer.

Abstract

75 Background: The two common therapies for metastatic castrate resistant prostate cancer (mCRPC), enzalutamide (ENZ) and abiraterone (AA), have different effectiveness in patients with diabetes mellitus and obesity due to different mechanisms of action, along with AA requiring the co-administration of prednisone. However, no prior study has assessed responses to treatment based on glycated hemoglobin (HbA1c) while accounting for body-mass index (BMI). Methods: Patients treated with AA or ENZ from September 10, 2014 to June 2, 2017 were identified within the Veterans Health Administration. The patients were classified by most recent HbA1c values (<5.6%, 5.6%-6.4%, 6.5%-7.1%, ≥7.2%) collected prior to the start of AA or ENZ. Kaplan Meier and Cox proportional hazards modeling was performed to assess the association between overall survival and covariates including age, Charlson Comorbidity Index, BMI, baseline PSA, and HbA1c. Results: 3421 veterans treated with AA or ENZ had HbA1c data available. 658 patients with HbA1c <5.6%, 1430 with 5.6-6.4%, 667 with 6.5%-7.1%, and 666 with HbA1c ≥7.2. Kaplan Meier analysis showed the following median survival in months with ENZ vs AA: <5.6% = 22.1 vs 24.5 (p = 0.04 by log-rank), 5.6%-6.4% = 27.7 vs 22.6 (p = 0.01), 6.5%-7.1% = 23.0 vs 19.8 (p = 0.005), ≥7.2% = 26.0 vs 21.0 (p = 0.04). Cox models showed no difference in median survival between ENZ vs AA in patients with HbA1c <5.6%, adjusted hazard ratio (aHR) 1.15 (95% CI, 0.960-1.370). However, there was significantly longer survival in patients who received ENZ compared to AA in all other groups as follows: 5.6%-6.4% aHR 0.86 (95% CI, 0.759-0.965), 6.5%-7.1% aHR 0.74 (0.623-0.879) and ≥7.2% aHR 0.80 (0.669-0.948). Additionally, in patients treated with AA, higher HbA1c values were associated with inferior survival compared to HbA1c <5.6%, aHR 1.40 (1.19-1.65) for 6.5-7.1% and aHR 1.25 (1.05-1.48) for ≥7.2%. Conclusions: In patients with HbA1c ≥5.6%, ENZ was associated with longer overall survival compared to AA, even when including baseline BMI. Additionally, in patients treated with AA, higher HbA1c values had inferior survivals compared to patients with HbA1c <5.6%. No difference in survival was observed across the HbA1c strata with ENZ. Further studies of interactions between patient factors and treatments are warranted to guide treatment selection for prostate cancer therapy.