Zytiga Effective Pre Chemotherapy

The results from the latest Phase 3 clinical trial on Zytiga pre chemotherapy are clear cut - there is a progression free survival increase (PFS) and a trend towards overall survival (OS). The exact extent of OS for Zytiga could not be determined since the mean OS has not been reached in the Zytiga arm of the study due to the actual extent of OS. The OS of the placebo arm was 27 months and for Zytiga was longer than this but how much longer we will not know since the trial has been completed. Dr Ryan estimates the OS to be about 33% which is a 9 month extension of life.

Here is the Abstract presented by Ryan et al at the ASCO meeting in Chicago on 2 June 2012

Interim analysis (IA) results of COU-AA-302, a randomized, phase III study of abiraterone acetate (AA) in chemotherapy-naive patients (pts) with metastatic castration-resistant prostate cancer (mCRPC).

Abstract:

Background: AA is an androgen biosynthesis inhibitor that inhibits CYP17 and improves overall survival (OS) in post-docetaxel mCRPC. The primary objective of COU-AA-302 was to compare clinical benefit of AA + prednisone (P) vs placebo (PL) + P in chemo-naive, asymptomatic/mildly symptomatic mCRPC pts.

Methods: 1088 pts (151 centers; 12 countries) were randomized 1:1 to AA (1 g) + P (5 mg BID) or PL + P. Co-primary endpoints: radiographic progression-free survival (rPFS) and OS. Median times estimated using K-M method including LR statistic for inference. The Lan-DeMets α-spending function was used for OS.

Results:The Independent Data Monitoring Committee concluded that the OS, rPFS and secondary endpoints (Table) all favored the AA arm and unanimously recommended unblinding the study and crossing pts from PL to AA at IA (43% of total events). Median follow up = 22.2 mos. Grade 3/4 AEs (AA + P, PL + P) (%): hypertension 3.9 vs 3.0; hypokalemia 2.4 vs 1.9; ALT↑ 5.4 vs 0.7; AST↑ 3.0 vs 0.9.

Conclusions:AA + P produced a statistically significant improvement in rPFS and a strong trend for increased OS at this IA. AA resulted in clinically and statistically significant effects on all secondary endpoints. IA results confirmed the acceptable tolerability/safety profile of AA. This is the first randomized trial to demonstrate both OS and rPFS benefits in chemo-naive mCRPC and that inhibition of persistent extragonadal androgen synthesis significantly delays initiation of cytotoxic chemo. While median OS (AA arm) has not been reached, median PL arm OS (27.2 mos) is the longest measured in any phase III mCRPC study.

	AA + P (median, mos)	PL + P (median, mos)	HR (95% CI)	P
rPFS*	NR	8.3	0.43 (0.35, 0.52)	<0.0001
OS†	NR	27.2	0.75 (0.61, 0.93)	0.0097
Time to opiate use (cancer-related pain)	NR	23.7	0.69 (0.57, 0.83)	0.0001
Time to chemotherapy initiation	25.2	16.8	0.58 (0.49, 0.69)	<0.0001
Time to ECOG-PS deterioration	12.3	10.9	0.82 (0.71, 0.94)	0.0053
Time to PSA progression	11.1	5.6	0.49 (0.42, 0.57)	<0.0001

Abbreviation: NR, not reached.