Ipilimumab Before Chemotherapy Fails To Boost mCRPC Overall Survival

Tumour activity but no significant overall survival extension with ipilimumab for chemotherapy-naïve metastatic castration-resistant prostate cancer patients

 medwireNews: Phase III trial results show tumour-directed activity but no overall survival (OS) benefit with ipilimumab over placebo for metastatic castration-resistant prostate cancer (mCRPC) patients without visceral disease, few or no symptoms and no prior chemotherapy.

The primary endpoint of median OS was 28.7 months for the 399 patients randomly assigned to receive up to four doses of ipilimumab 10 mg/kg every 3 weeks followed by a 10 mg/kg maintenance dose every 3 months in the absence of progression.

This did not significantly differ from the median OS of 29.7 months achieved by the 199 patients who were given a placebo, the CA184-095 investigators report in the Journal of Clinical Oncology.

However, Tomasz Beer, from the Knight Cancer Institute in Portland, Oregon, USA, and co-authors say that progression-free survival (PFS) was better in the ipilimumab-treated patients, at a median of 5.6 versus 3.8 months with placebo, giving a significant hazard ratio of 0.67.

In addition, exploratory analysis gave a significantly better prostate-specific antigen (PSA) response rate with ipilimumab than placebo (23 vs 8%), which, together with the PFS result, “suggests antitumour activity of ipilimumab in some chemotherapy-naïve patients with mCRPC without visceral metastases”, they write.

The researchers note that these results are consistent with those from the CA184-043 trial, which found that ipilimumab 10 mg/kg given after a single dose of bone-direct radiotherapy in mCRPC patients previously treated with chemotherapy significantly improved PFS and PSA response but not OS compared with placebo.

But the current results do not support the hypothesis generated by the earlier study that patients without visceral metastases may respond better to ipilimumab, they add.

Toxicity in the current trial was “clinically relevant, but largely manageable” and similar to that previously reported in patients given ipilimumab after chemotherapy, the authors write, with the most common treatment-related adverse events including diarrhoea, rash, pruritus, fatigue, nausea, reduced appetite and vomiting.

“Two large randomized trials have now conclusively demonstrated that treatment with ipilimumab does not extend OS in unselected populations of patients with mCRPC but does result in measurable antitumor activity”, the team concludes.

“Future work should be directed at determining how to harness such antitumor activity, potentially through identification of biomarkers that may enable prediction of benefit from treatment with ipilimumab”, the researchers recommend.

“Based on current evidence, a potential role for newer immune checkpoint inhibitors, such as nivolumab and pembrolizumab, and other immunostimulatory strategies, either as single agents or in combination therapy, remains to be defined in patients with mCRPC.”


Beer TM, Kwon ED, Drake CG, et al. Randomized, double-blind, phase III trial of ipilimumab versus placebo in asymptomatic or minimally symptomatic patients with metastatic chemotherapy-naive castration-resistant prostate cancer. J Clin Oncol; Advance online publication 10 October 2016. doi: 10.1200/JCO.2016.69.1584

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