There have been many potential targets identified for the treatment of advanced prostate cancer. Many of these targets are being actively explored with clinical trials designed to test some inhibitors of the targets.
Antisense oligonucleotides (OGX-011) targets clusterin, a chaperone protein and OGX-427 which targets heat-shock protein 27 are among the inhibitors being evaluated.
OGX-011 was tested with docetaxel (chemotherapy) in a randomized phase II trial. The results of the trial reported better overall survival in the combination arm (median, 23.8 and 16.9 months, respectively).28 Two additional phase III trials are ongoing to confirm these results in combination with chemotherapy: one in the first-line setting (SYNERGY, testing docetaxel with or without custirsen, NCT01188187), the other in the second-line setting (AFFINITY, testing cabazitaxel with and without custirsen, NCT01578655).
OGX-427 was tested in a randomized phase II trial compared with prednisone with, respectively, 71% and 40% of men alive and free of progression at 12 weeks, and activity also reported in terms of PSA response, RECIST criteria, and circulating tumor cell conversion. (1)
Another potential treatment, tasquinimod targets S100A9. This oral compound was tested in a randomized phase II trial in 201 asymptomatic men with mCRPC. The primary endpoint, progression free survival (PFS) was significantly improved (7.6 vs. 3.3 months; p = 0.0042)(2). There is a confirmatory phase III trial ongoing at this time.
Additionally, there is a proof-of-concept “switch maintenance” randomized study ongoing with tasquinimod in men with disease response or stabilization on first-line docetaxel chemotherapy (NCT01732549).
In combination with the many inhibitors I discussed in the post of June 21, 2013 we should take heed that there are many potential new treatments coming down the pike, or on the horizon.
(1) – Chi KN, Hotte SJ, Ellard S, et al. A randomized phase II study of OGX-427 plus prednisone (P) versus P alone in patients (pts) with metastatic castration resistant prostate cancer (CRPC). J Clin Oncol.2012;30 (suppl; abstr 4514).
(2) – Pili R, Häggman M, Stadler WM, et al. Phase II randomized, double-blind, placebo-controlled study of tasquinimod in men with minimally symptomatic metastatic castrate-resistant prostate cancer. J Clin Oncol.2011;29:4022-4028.
Joel T Nowak, M.A., M.S.W.