In a poster presentation at the recent European Society of Medical Oncologists (ESMO) there was a very interesting poster presented updating a phase 3 clinical trial (CA184-043) which evaluated the overall survival (OS) with radiotherapy (RT) followed by either the immunologic drug Ipilimumab (Ipi) or with a placebo. This trial did not meet its endpoint and was considered to have failed (Kwon ED, et al. Lancet Oncol 2014 in press), but it still remains of significant interest. The update included an additional year of data.

In the trial 799 men were randomized to receive a single dose of radio therapy to their bone metastases followed by either Ipi (N = 399) or placebo (N = 400). An updated overall survival analysis was performed.

Updated OS analysis with survival rates up to 3 years was consistent with the primary analysis. Also consistent with previous reports, pre-specified subgroup analyses suggest greater activity in men with lower disease burden

[e.g., Ipi vs. placebo with (HR 1.17, 0.89–1.53) or without (0.74, 0.61–0.89) visceral metastases].

The safety profile with extended follow-up was similar to that reported previously, which included immune-related AEs (irAEs) (gastrointestinal, dermatologic, endocrine, and hepatic). Most irAEs were manageable with established Ipi treatment algorithms.

With an additional year of follow-up, the activity observed for Ipi + RT in post-docetaxel mCRPC pts 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) will be evaluated in the ongoing phase 3 study, CA184-095.

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.

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.