Comprehensive Cancer Centers of Nevada, Las Vegas, NV
Oscar B. Goodman Jr., Thomas W. Flaig , Arturo Molina , Peter Mulders , Henrik Suttmann , Jinhui Li , Thian San Kheoh , Johann Sebastian De Bono , Howard I. Scher
Background: VD is a negative prognostic factor in mCRPC patients (pts) and may be less responsive to hormonal therapy. AA, a selective androgen biosynthesis inhibitor, inhibits androgen synthesis from adrenal and intratumoral sources. Improved overall survival (OS) with AA vs prednisone (P) was demonstrated in a randomized trial of pts with mCRPC post-docetaxel (D). Here we further assess the effect of AA on OS and other clinical outcomes in post-D mCRPC pts with VD (liver or lung, but not nodal-only metastases). Methods: In COU-AA-301, pts with mCRPC previously treated with D were randomized 2:1 to AA (1000 mg) + P (5 mg BID) (n=797) or placebo + P (n=398). The primary end point was OS. Data shown herein represent the updated analysis (775 events) of patients with (n=352) or without (n=843) VD. Results: The OS benefit of AA was similarly improved in patients with VD (4.6 m) and without VD (4.8 m) (Table). Treatment with AA led to significant 40% and 32% reductions in the risk of radiographic progression or death in patients with VD or without VD, respectively. Soft-tissue objective response rates were superior with AA in both groups. PSA response rates (50% reduction) were significantly improved by AA in both groups. Grade 3/4 adverse events (AEs) were similar in both groups. Hypertension, hypokalemia, and LFT abnormalities were observed with AA in pts with and without VD. Conclusions: AA has substantial anti-tumor activity and provides clinical benefit including improvements in OS and rPFS in post-D mCRPC pts with VD indicating it is a therapeutically active treatment option for CRPC pts. Safety/tolerability of AA in pts with VD was similar to that reported previously in mCRPC. Clinical trial information: NCT00638690.
Pts with VD |
Pts without VD |
|||||
---|---|---|---|---|---|---|
AA (N=253) |
P (N=99) |
P values | AA (N=544) |
P (N=299) |
P values | |
OS, median (m) HR (95% CI) |
12.9 | 8.3 | p=0.1022 0.79 (0.60, 1.05) |
17.1 | 12.3 | p<0.0001 0.69 (0.58, 0.83) |
rPFS, median (m) HR (95% CI) |
5.6 | 2.8 | p=0.0002 0.60 (0.46, 0.78) |
5.9 | 5.1 | p<0.0001 0.68 (0.58, 0.80) |
PSA response rate | 28% | 7% | p<0.0001 | 30% | 5% | p<0.0001 |
Objective response rate Relative risk (95% CI) |
11% | 0% | NE | 19% | 5% | 3.51 (1.53, 8.04) |
Grade 3/4 AEs | 62% | 65% | 60% | 60% |
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