Study Finds PFS Benefit, but No Overall Survival Benefit, for Ipilimumab in Metastatic Castration-Resistant Prostate Cancer


Key Points

  • Ipilimumab did not improve overall survival vs placebo in men with asymptomatic or minimally symptomatic chemotherapy-naive metastatic castration-resistant prostate cancer without visceral metastases.
  • Ipilimumab was associated with prolonged progression-free survival and higher PSA response rate.

Ipilimumab (Yervoy) was associated with prolonged progression-free survival—but not overall survival—compared with placebo in men with asymptomatic or minimally symptomatic chemotherapy-naive metastatic castration-resistant prostate cancer without visceral metastases, according to a phase III trial reported by Beer et al in the Journal of Clinical Oncology.

Study Details

In this double-blind trial, 598 patients from sites in Europe, North and South America, and Australia were randomized 2:1 beginning in July 2010 to receive ipilimumab at 10 mg/kg (n = 399) or placebo (n = 199) every 3 weeks for up to 4 doses, with ipilimumab at 10 mg/kg or placebo maintenance given to patients without disease progression every 3 months. The primary endpoint was overall survival in the intent-to-treat population.

Patients had a median age of approximately 69 years (68%–74% ≥ 65 years), and most had an Eastern Cooperative Oncology Group performance status of 0 (75% in both groups) and bone metastases (78%–79%). Gleason score was ≥ 8 in 45% to 48% of patients, and median prostate-specific antigen (PSA) levels were 41.2 mg/L in the ipilimumab group and 49.5 mg/L in the placebo group.

Survival Outcomes

The trial database was locked in August 2015, with a total of 380 overall survival events reported. At the time of the primary overall survival analysis, all patients had been followed for at least 2 years, 85% had been followed for 3 years, and 26% had been followed for 4 years. Median overall survival was 28.7 months (95% confidence interval [CI] = 24.5–32.5 months) in the ipilimumab group vs 29.7 months (95% CI = 26.1–34.2 months) in the placebo group (hazard ratio [HR] = 1.11, P = .3667).

Median progression-free survival was 5.6 months vs 3.8 months (HR = 0.67, 95.87% CI = 0.55–0.81). Subsequent systemic treatment with chemotherapy, hormonal therapy, or immunotherapy was received by 67% of ipilimumab patients and 79% of placebo patients. Ipilimumab patients had a longer time to systemic nonhormonal cytotoxic therapy (HR = 0.65, 95.% CI = 0.52–0.83) and to docetaxel therapy (HR = 0.70, 95% CI = 0.55–0.88). An exploratory analysis showed a higher PSA response rate with ipilimumab (23% vs 8%).

Adverse Events

The most common treatment-related adverse events of any grade in the ipilimumab group were diarrhea (43%), rash (33%), pruritus (27%), and fatigue (24%). Grade 3 or 4 treatment-related adverse events occurred in 40% vs 6% of patients, with diarrhea (15%) being the only event occurring in > 3% of the ipilimumab group. Immune-related events of any grade occurred in 77% vs 29% of patients and were of grade 3 or 4 in 31% vs 2%.

Discontinuation due to treatment-related adverse events occurred in 29% vs 3%. Death due to treatment-related events occurred in nine ipilimumab patients (2%), with causes consisting of cardiac arrest (n = 2), gastrointestinal perforation, renal failure, hepatitis, pneumonitis, multiorgan lymphatic infiltration resulting in cardiac arrest, pneumonia, and hepatotoxicity.

The investigators concluded: “Ipilimumab did not improve [overall survival] in patients with metastatic castration-resistant prostate cancer. The observed increases in progression-free survival and prostate-specific antigen response rates suggest antitumor activity in a patient subset.”

The study was supported by Bristol-Myers Squibb.

Tomasz M. Beer, MD, of Oregon Health & Science University Knight Cancer Institute, is the corresponding author of the Journal of Clinical Oncology.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.