A total of 1577 patients with mCRPC from three phase III randomized controlled trials (VENICE, ASCENT2 and MAINSAIL) were analyzed in this study. All patients were mCRPC with ECOG status less than or equal to 2, with no prior chemotherapy. The primary endpoint was overall survival and the secondary endpoint was the rate of adverse events during administration of chemotherapy, and treatment discontinuation. The predictive role of BMI in overall survival and adverse events was analyzed using Cox proportional hazards regression model, after adjusting for age, PSA, ECOG status, number of metastasis, prior treatment and chemotherapy dosage. BMI was analyzed both as a categorical and as a continuous variable. For this study, a patient with a BMI of >30 kg/m2 was defined as obese.
The results in this study demonstrated that the median (IQR) age of the patients in this study was 69 (63, 74) years with a median BMI of 28 kg/m2 (25-31). A total of 6 patients had a BMI <20, 355 had BMI between 20-25, 732 had a BMI between 25-30 and 474 had a BMI of over 30 km/m2. By the end of the study, 655 patients had died. The median follow-up for the surviving patients was 12 months. The 12- , 24-, and 36-month survival probabilities were 79% (95% CI 76%-81%), 45% (95% CI 42-48%), and 23% (95% CI 20%-27%), respectively.
The Cox proportional hazard models demonstrated that BMI was a protective factor of overall survival both as a continuous variable (HR:0.96; 95%CI: 0.94, 0.99; p=0.015); and as a categorical variable (HR:0.71, 95%CI: 0.53, 0.96; p=0.027). This can be seen graphically in the Kaplan Meyer curve in Figure 1.
During treatment 822 adverse events had occurred. The median time to adverse events was 5.8 months. The 12-, 24- and 36- month event free probabilities were 48% (95% CI 45-51%), 41% (95% CI 38-44%). And 37% (95% CI 33-41%), respectively. Importantly BMI did not manifest as a significant predictor of adverse events, whether regarded as a continuous or as a categorical variable (p>0.8). When predicting treatment discontinuation, BMI did not emerge as a statistically significant predictor when investigated as a continuous (p=0.7) or a categorical value (p>0.4)
The authors of this study concluded that BMI is a significant predictor of overall survival in patients with mCRPC, but not of adverse events. In other words, obese and overweight patients with mCRPC present a higher survival probability when compared to normal weight patients. Importantly, high BMI did not emerge as a significant predictor for treatment discontinuation or adverse events. Lastly, by excluding any interaction between chemotherapy dose and BMI the protective effect of high BMI was not demonstrated to be related to the higher chemotherapy dose, when trying to predict overall survival.
Speaker: Alberto Martini, Icahn School of Medicine at Mount Sinai, New York City, New York
Written by: Hanan Goldberg, MD, Urologic Oncology Fellow, SUO, University of Toronto, Princess Margaret Cancer Centre, @GoldbergHanan, at the 19th Annual Meeting of the Society of Urologic Oncology (SUO), November 28-30, 2018 – Phoenix, Arizona