Reporting both negative clinical trial results is as important as reporting positive results. However, pharmaceutical companies often bury negative results.

Fortunately (actually unfortunately because there were negative results) a Phase III, randomized, double-blind, multicenter trial comparing orteronel (TAK-700) plus prednisone with placebo plus prednisone in men with metastatic castration-resistant prostate cancer (mCRPC) that has progressed during or after docetaxel-based therapy failed to meet its endpoints, or has failed.

The study included 1,099 men with advanced prostate cancer who were randomly assigned in a 2:1 schedule to receive TAK-700. The primary end point was overall survival (OS). Key secondary end points which were to be analyzed only if the primary end point was achieved included radiographic progression-free survival

[rPFS], greater than or equal to a 50% decrease of prostate-specific antigen (PSA) and pain response at 12 weeks.

RESULTS: The study was un-blinded after crossing a pre-specified OS futility boundary. The median OS was 17.0 months versus 15.2 months with TAK-7700 and prednisone versus placebo and prednisone.

Improved rPFS was observed with the investigational group (median, 8.3 v 5.7 months). The investigational group also showed advantages over placebo-prednisone in PSA and time to PSA progression but not pain response rate.

Additionally, adverse events (all grades) were generally more frequent with with the TAK-700 investigational group.

CONCLUSION: TAK-700 did not meet the primary end point of overall survival (OS). However, some anti-tumor response was noted by a longer rPFS and a higher lower PSA rate.

J Clin Oncol. 2015 Mar 1;33(7):723-31.
doi: 10.1200/JCO.2014.56.5119 Fizazi K, Jones R, Oudard S, Efstathiou E, Saad F, de Wit R, De Bono J, Cruz FM, Fountzilas G, Ulys A, Carcano F, Agarwal N, Agus D, Bellmunt J, Petrylak DP, Lee SY, Webb IJ, Tejura B, Borgstein N, Dreicer R.

PMID: 25624429

Joel T. Nowak, M.A., M.S.W.