In mCRPC, BMI remains an important predictor of survival

Compared to those who are overweight or of normal weight, obese patients are more likely to have better disease-specific and overall survival (OS) in metastatic castration-resistant prostate cancer (mCRPC), according to the results of an analysis of three Phase 3 clinical trials that were presented at the 2021 American Urological Association annual meeting.¹

“The effect of BMI on cancer-specific mortality has also been confirmed as a continuous and categorical variable,” said study co-author Giuseppe Ottone Cirulli, MD, resident in urology at the University. Vita-Salute San Raffaele from Milan, Italy. “Also, the protective effect of BMI is not related to the higher dose of chemotherapy.”

Cirulli said previous data has demonstrated the correlation between BMI and survival outcomes in prostate cancer. In this study, researchers sought to determine whether BMI in patients with mCRPC is associated with OS and disease-specific mortality.

Researchers identified 1,577 patients in the ASCENT2 (NCT00273338), MAINSAL (NCT00988208) and VENICE (NCT00519285) trials, of which 655 had died at the end of the studies. The median follow-up of survivors was 12 months. Cox’s semi-proportional risk model was used to predict OS, while concurrent risk regression was used to predict cancer mortality.

There were analyzes adjusted for age, prostate specific antigen, ECOG, number of metastases, and previous treatment.

The median age was 69 years and the median BMI was 28 kg / m2. The researchers analyzed the role of BMI on survival outcomes both as a continuous and categorical variable (<20 vs 20-25 vs 25-30 vs >30 km / m2). A BMI of 30 kg / m2 or more was considered obese.

BMI appeared to be a protective factor for OS both as a continuous variable (HR: 0.96; P = 0.015) and as a categorical variable (HR: 0.71; P = .027). Likewise, the effect of BMI on cancer-specific mortality was confirmed both continuously (HR, 0.94; P = 0.002) and as a categorical variable (HR: 0.65; P = .018).

Cirulli and colleagues selected patients from ASCENT2, MAINSAL, and VENICE because all 3 included males with mCRPC treated with docetaxel. The chemotherapy dose is determined in part by weight, but the investigators determined that there was no interaction between the BMI categories and the docetaxel dose (all P > .05).

In ASCENT2, patients were randomized to receive 45 mcg of DN-101, 36 mg / m2 of docetaxel, and 24 mg of dexamethasone per week for 3 weeks of a 4-week cycle (n = 476) or 5 mg of prednisone twice daily plus 75 mg / m2 docetaxel and 24 mg dexamethasone every 3 weeks (n = 477).²

The median follow-up of living patients at the last assessment was 11.7 months. The median OS was 17.8 months (95% CI, 16.0-19.5) in the experimental arm and 20.2 months (95% CI, 18.8-23.0) in the experimental arm. control (log-rank P = .002). Survival remained lower in the experimental arm even after adjusting for basic variables (RR: 1.33; P = .019).

In MAINSAL, chemotherapy-naïve patients with progressive mCRPC were randomized to receive 75 mg / m2 docetaxel on day 1 and 5 mg prednisone twice daily on days 1 to 21 and 25 mg lenalidomide once daily (n = 533) or placebo once daily (n = 526) on days 1-14 of each 21-day treatment cycle.³

The median OS was 17.7 months (95% CI, 14.8-18.8) in the lenalidomide group and was not achieved in the placebo group (RR: 1.53; 95% CI, 1.17-2.00; P = 0.0017). The trial was then closed prematurely due to its futility.

In VENICE, 1224 chemotherapy-naïve patients with adequate organ function received 75 mg / m2 docetaxel every 3 weeks plus 5 mg oral prednisone twice daily (5 mg twice daily). They were then randomized to receive 6 mg / kg aflibercept (Eylea; n = 612) or placebo (n = 612) every 3 weeks. The results showed that the median OS was 22.1 months (95.6 CI, 20.3-24.1) in the aflibercept group vs 21.2 months (95.6% CI, 19.6-23, 8) in the placebo group (HR, 0.94; 95.6% CI, 0.82-1.08; P = .38).⁴

_{The references}

• _{Martini A, Cirulli GO, Gandaglia G, et al. The obesity paradox in metastatic castration-resistant prostate cancer. Presented at: the 2021 American Urological Association Annual Meeting; September 10-13, 2021; virtual. Abstract PD05-01.}

• _{Scher HI, Jia X, Chi K et al. Randomized, open-label phase III trial comparing high-dose docetaxel plus calcitriol versus docetaxel plus prednisone in patients with castration-resistant prostate cancer. J Clin Oncol. 2011; 29 (16): 2191-2198. doi: 10.1200 / JCO.2010.32.8815}

• _{Petrylak DP, Vogelzang NJ, Budnik N, et al. Docetaxel and prednisone with or without lenalidomide in chemotherapy-naïve patients with metastatic castration-resistant prostate cancer (MAINSAIL): a randomized, double-blind, placebo-controlled phase 3 trial. Lancet Oncol. 2015, 16 (4): 417-425. doi: 10.1016 / S1470-2045 (15) 70025-2}

• _{Tannock IF, Fizazi K, Ivanov S, et al. Aflibercept versus placebo in combination with docetaxel and prednisone for the treatment of men with metastatic castration-resistant prostate cancer (VENICE): a randomized phase 3 double-blind trial. Lancet Oncol. 2013; 14 (8): 760-768. doi: 10.1016 / S1470-2045 (13) 70184-0}