Ipilimumab Prostate Cancer Results Revealed

Monoclonal antibody against metastatic prostate cancer shows signs of activity despite no overall survival benefit

medwireNews: Phase III trial results have failed to demonstrate a significant gain in overall survival for metastatic prostate cancer patients treated with a Monoclonal antibody against cytotoxic T-lymphocyte Antigen 4 (CTLA-4) compared with placebo.

Median overall survival for the 399 men randomly assigned to receive a single 8 Gy fraction of radiation directed to bone followed by ipilimumab 10 mg/kg was 11.2 months compared with 10.0 months for the 400 patients who received radiotherapy plus placebo, reflecting a nonsignificant difference.

Nevertheless, the researchers say there are “signs of activity” that suggest men with castration-resistant prostate cancer and at least one bone metastasis whose disease progresses after docetaxel may benefit from bone-directed radiotherapy plus ipilimumab.

In particular, the hazard ratio for overall survival for patients treated with ipilimumab versus placebo fell over time, from 1.46 for the first 5 months of follow-up to 0.65 for months 5 to 12 and 0.60 after 12 months.
And further analysis revealed that ipilimumab was more active in patients with favourable prognostic features than those with a poorer prognosis, say Eugene Kwon, from the Mayo Clinic in Rochester, Minnesota, USA, and co-authors.

Among patients without visceral metastases, an alkaline phosphatase concentration within 1.5 times the upper limit of normal and a haemoglobin level of at least 110 g/L, the 146 patients who received ipilimumab had a median overall survival of 22.7 months compared with 15.8 months for the 142 receiving placebo.

Ipilimumab also significantly improved progression-free survival, at a median of 4.0 months versus 3.1 months for controls, and patients treated with the monoclonal antibody were more likely to achieve a 50% or greater reduction in prostate-specific antigen (PSA, 13.1 vs 5.2%).

“Although prolongation of progression-free survival in this population […] could be a reflection of immune-mediated responses against prostate cancer cells, additional studies will be necessary to assess whether the antitumour clinical activity seen in the present study is indeed immune related, tumour specific, and consistent with the putative mechanism of action of ipilimumab (ie, CTLA-4 blockade)”, the team writes in The Lancet Oncology.

In an accompanying comment, Chris Parker, from the Royal Marsden Hospital in Sutton, UK, says that improved efficacy in men with favourable prognostic features is “plausible” because of the small disease volume in such patients.

Noting that ongoing immunotherapy trials for prostate cancer also include a phase III investigation into a poxviral PSA vaccine, he concludes: “The knowledge that manipulation of the immune system can improve survival of men with prostate cancer provides hope that one or both of these approaches will prove to be a real step forward in clinical practice.”

Reference

Kwon E, Drake C, Scher H, et al. Ipilimumab versus placebo after radiotherapy in patients with metastatic castration-resistant prostate cancer that had progressed after docetaxel chemotherapy (CA184-043): a multicentre, randomised, double-blind, phase 3 trial. Lancet Oncol 2014; Early Online Publication 13 May. doi:10.1016/S1470-2045(14)70189-5

Parker C. A near miss for prostate cancer immunotherapy. Lancet Oncol; 13 May 2014.

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