In a phase III trial, ipilimumab increased the overall survival of men with advanced castration-resistant prostate cancer when used with a single dose of radiotherapy by 1.2 months, but the results were not statistically significant.
Ipilimumab increased the overall survival of men with advanced castration-resistant prostate cancer (CRPC) when used with a single dose of radiotherapy by 1.2 months, but the results were not statistically significant. The phase III trial had randomized advanced CRPC patients to either ipilimumab or placebo following a dose of radiotherapy. All patients had previously been treated with the chemotherapy docetaxel.
Although the overall survival in the 799-patient trial was not a significant improvement, the investigators concluded that these phase III results “support activity of ipilimumab in advanced CRPC.”
“Although the primary endpoint was not met, the subgroup analysis did suggest a benefit for patients with less advanced disease,” said Howard Scher, MD, chair in urologic oncology at Memorial Sloan-Kettering Cancer Center, New York, and one of the authors of the trial. “This is consistent with what has been seen with biologic therapies in other types of cancer.”
The results were released as an abstract ahead of a presentation at the upcoming 2013 European Cancer Congress by lead study author Winald Gerritsen, MD of Nijmegen Medical Center in Nijmegen, Netherlands in late September.
The median overall survival in the ipilimumab-treated patient arm was 11.2 months compared to 10 months in the placebo arm (hazard ratio [HR] = 0.85, P = .053). Progression-free survival was significantly improved (HR = 0.70) according to the abstract. More patients treated with ipilimumab had at least a 50% decrease in prostate-specific antigen levels compared to those in the placebo arm (13.1% vs 5.3%, respectively).
Patients were randomized 1:1 and treated with bone-directed radiotherapy followed by placebo of 10 mg/kg ipilimumab every 3 weeks for 4 cycles followed by maintenance therapy every 3 months.
A pre-specified analysis suggests that a subset of patients with no evidence of visceral disease and favorable laboratory test levels may be most responsive to ipilimumab. Further details are expected during the presentation at the European meeting.
Prostate cancer patients treated with ipilimumab had similar adverse events related to ipilimumab as those treated for melanoma. Adverse events more frequent in the treatment arm were immune-related, including gastrointestinal toxicity, elevated liver enzyme levels, and endocrine and skin toxicities. Drug-related deaths and gastrointestinal perforations were 1% in the ipilimumab arm compared to 0.6% in the placebo arm.
Ipilimumab, manufactured by Bristol-Myers Squibb, is currently approved for treatment of metastatic melanoma. An international ipilimumab phase III trial in asymptomatic or minimally symptomatic CRPC patients who are chemotherapy-naive is still ongoing. That trial is comparing a 10 mg/kg dose of ipilimumab to placebo in approximately 600 patients.
It is anticipated that the patients enrolled in this pre-chemotherapy trial will have less advanced disease. These pre-chemotherapy patients are also less exposed to corticosteroids, which can potentially reduce the effect of a biologic therapy, said Scher.