Castate resistant metastatic prostate cancer (mRPC) withvisceral disease (tumors involving the internal organs of the body, specifically those within the chest (as the heart or lungs) or abdomen (as the liver, pancreas or intestines) is a negative prognostic factor.
In many cases clinical trials of new investigational drugs rule out men with visceral disease from the trial sample. This often results in the FDA approved label specifically excluding men with visceral disease. This makes it very easy for insurance companies to refuse to pay for these drugs in men with visceral disease since this is technically an “off label” use.
There was an exploratory analysis of the COU-AA-301 clinical trial of abiraterone acetate (Zytiga) that assessed whether Zytiga improved overall survival (OS) in mCRPC men with visceral disease in the post chemotherapy (docetaxel) stage of treatment.
In the COU-AA-301trial, men who had failed or stopped chemotherapy (docetaxel) were randomized 2:1 to Zytiga 1000?mg (n=797) or placebo (n=398) once daily, each with prednisone 5?mg b.i.d.
The primary end point of the trial was overall survival (OS) and the secondary end points included radiographic progression-free survival (rPFS), PSA response rate and objective response rate (ORR).
The treatment effects in visceral disease (n=352) and non-visceral disease (n=843) subsets were examined using final data (775 OS events).
The analysis showed that men receiving Zytigaplus prednisone produced similar absolute improvement in median OS. men with visceral disease (4.6 months) and without (4.8 months) versus prednisone alone; hazard ratios (HRs) were 0.79 (95% confidence interval (CI): 0.60-1.05; P=0.102) and 0.69 (95% CI: 0.58-0.83; P< 0.0001), respectively.
In addition, the treatment with Zytiga plus prednisone significantly and comparably improved secondary endpoint outcomes versus only prednisone in both the subsets: the HRs for rPFS were 0.60 (95% CI: 0.46-0.78; P=0.0002) and 0.68 (95% CI: 0.58-0.80; P< 0.0001) in visceral and non-visceral disease subsets, respectively.
PSA response rates were 28% versus 7% in the visceral disease subsets and 30% versus 5% in the non-visceral disease subsets (both P< 0.0001), and ORRs were 11% versus 0% (P=0.0058) and 19% versus 5% (P=0.0010), respectively.
The incidence of grade 3/4 adverse events was similar between the subsets and between the treatment arms in each subset. Adverse events related to CYP17 blockade were increased in the Zytiga arms and were similar in patients with or without visceral disease.
It was concluded that Zytiga plus prednisone provides significant clinical benefit, including improvements in OS and secondary end points, in post-docetaxel mCRPC patients with or without baseline visceral disease. The presence of visceral disease does not preclude clinical benefit from Zytiga and should be considered by a treating physican.
Goodman OB Jr, Flaig TW, Molina A, Mulders PF, Fizazi K, Suttmann H, Li J, Kheoh T, de Bono JS, Scher HI.
Department of Medical Oncology, Comprehensive Cancer Centers of Nevada, Las Vegas, NV, USA.
Reference: Prostate Cancer Prostatic Dis. 2013 Oct 1. Epub ahead of print.
Joel T. Nowak, M.A., M.S.W.