Presented in a poster at the recent European Society of Medical Oncologist (ESMO) there was a data update of the phase 3 clinical trial (CA184-043) which evaluated overall survival (OS) in men having radiotherapy (RT) followed by either the immunologic drug Ipilimumab (Ipi) or with a placebo. Initially, this trial did not meet its endpoint and was considered to have failed (Kwon ED, et al. Lancet Oncol 2014 in press). This update included an additional year of data.

In the trial 799 men were randomized to receive a single dose of RT to their bone metastases followed by either Ipi (N = 399) or placebo (N = 400).

An updated overall survival (OS) analysis was consistent with the primary analysis. Also consistent with previous reports, pre-specified subgroup analyses suggest greater activity in men with a lower disease burden or without visceral metastases.

The safety profile with extended follow-up was similar to that reported previously, which included immune-related side effects, including gastrointestinal, dermatologic, endocrine, and hepatic problems. Most of these side effects were manageable.

With an additional year of follow-up, the activity observed for Ipi + RT in post-docetaxel mCRPCmen is maintained. In addition, subgroup analyses suggest men with lower disease burden may be more likely to benefit from Ipi treatment. Long-term OS and Ipi benefit in mCRPC men with lower disease burden (i.e., no visceral metastases) needs to be evaluated in this ongoing phase 3 study before any conclusions can be drawn as to the efficacy of the Ipi post radiotherapy.

These results are not surprising and are totally consistent with what we have learned about immune therapy. IT TAKES TIME TO WORK, so men with lower disease burdens will survive longer allowing the immune therapy the time it requires to become active and effective. This is why treatments like Provenge should be taken as soon as a man becomes castrate resistant, while their disease burden is lower.

I remain very optimistic; actually I should say hopeful, that Ipi will prove itself to be of value by extending overall survival in men with advanced prostate cancer. However, we need to wait the additional time that immunotherapy requires for us to see evidence of an increased survival advantage.

Annals of Oncology (2014) 25 (suppl_4): iv255-iv279. 10.1093/annonc/mdu336; K. Fizazi1, C.G. Drake2, E.D. Kwon3, A. Bossi4, A.J. van den Eertwegh5, H.I. Scher6, T.M. Beer7, M.B. McHenry8, D. Liu8, W.R. Gerritsen9, C. Logotheti

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