No Overall Survival Benefit With Addition of Sunitinib to Prednisone in Metastatic Castration-Resistant Prostate Cancer


Key Points

  • The addition of sunitinib to prednisone did not improve overall survival.
  • A benefit of sunitinib in progression-free survival was observed.
  • Toxicity was greater with sunitinib vs placebo.

In a phase III trial reported in the Journal of Clinical Oncology, Michaelson et al assessed the addition of the antiangiogenesis agent sunitinib (Sutent) to prednisone in patients with progressive metastatic castration-resistant prostate cancer after docetaxel-based chemotherapy. No significant improvement in overall survival was observed with the addition of sunitinib.

Study Details

In this double-blind, placebo-controlled trial, 873 patients were randomly assigned 2:1 to receive prednisone at 5 mg twice daily and either sunitinib at 37.5 mg/d continuously (n = 581) or placebo (n = 285). The primary endpoint was overall survival. Two interim analyses were planned.

The sunitinib and placebo groups were balanced for age (median, 69 and 68 years), Eastern Cooperative Oncology Group performance status (0 and 1 in 50% and 50% in both), Gleason score (8–10 in 51% and 45%, ≤ 6 in 13% and 15%), disease progression (prostate-specific antigen progression only in 54% and 50%, radiographic progression in 46% and 50%), prior VEGF inhibitor therapy (2% in both), number of prior systemic therapies (one in 86% in both, two in 10% and 11%), and reason for stopping docetaxel (progression in 91% and 92%, intolerance in 9% and 8%).

No Overall Survival Benefit

The study was stopped early after a second interim analysis indicated that an overall survival difference between groups was statistically improbable. After median follow-up of 8.7 months, median overall survival was 13.1 months in the sunitinib group vs 11.8 months in the placebo group (hazard ratio [HR] = 0.914,  P = .168). Progression-free survival was significantly longer in the sunitinib group (median, 5.6 vs 4.1 months, HR = 0.725,  P < .001). The objective response rate (no complete responses) was 6% vs 2% (odds ratio [OR] = 3.56, P = .040) and the stable disease rate was  26% vs 30%.


Treatment-related adverse events of any grade were more common in the sunitinib group (94% vs 62%), with the most common nonhematologic adverse events being diarrhea (41% vs 9%), decreased appetite (35% vs 12%), nausea (35% vs 12%), fatigue (30% vs 15%), hand-foot syndrome (29% vs 3%), dysgeusia (28% vs 8%), and vomiting (25% vs 7%). The most common grade 3 or 4 adverse events were fatigue (9% vs 1%), asthenia (8% vs 2%), and hand-foot syndrome (7% vs 0%).

Bone pain (12% vs 16%) and back pain (15% vs 21%) of any cause were less common with sunitinib. Grade 1 or 2 hematologic abnormalities were much more common with sunitinib, and rates of grade 3 or 4 hematologic abnormalities were 9% vs 8% for anemia, 3% vs <1% for leukopenia, 6% vs <1% for neutropenia, 20% vs 11% for lymphopenia, and 4% vs 1% for thrombocytopenia. 

Sunitinib dose reduction was required in 32% of patients, with the most common adverse events leading to dose reduction or delay being hand-foot syndrome (11%) and diarrhea, fatigue, and asthenia (9% each). Adverse events led to study drug discontinuation in 27% of the sunitinib group (most commonly due to fatigue and asthenia) and 7% of the placebo group.

A total of 57 patients (10%) in the sunitinib group and 30 patients (11%) in the placebo group died during the study, with most deaths (72% and 80%) due to prostate cancer. Death occurred due to pneumonia in one patient in each group, sepsis in two sunitinib patients, and cardiopulmonary arrest in one patient in each group. Death due to unknown causes occurred in 11% of the sunitinib group vs 0% in the placebo group.

Role of Antiangiogenesis Treatment?

As related by the authors, the findings are similar to those in another recently reported study (Cancer and Leukemia Group B 90401), which showed that the addition of the antiangiogenic agent bevacizumab (Avastin) to docetaxel and prednisone improved progression-free survival without improving overall survival in metastatic castration-resistant prostate cancer. They noted, “The reason that improved [progression-free survival] does not appear to translate to [overall survival] benefit with antiangiogenic agents is not clear. The magnitude of [progression-free survival] may be too small to affect [overall survival], or other factors may be involved.”

The investigators concluded: “The addition of sunitinib to prednisone did not improve [overall survival] compared with placebo in docetaxel-refractory [metastatic castration-resistant prostate cancer]…. Antiangiogenic agents may yet have a role to play in treating patients with [metastatic castration-resistant prostate cancer], but their future development in this area will require enhanced patient selection by using predictive biomarkers of response to guide therapy in a rational manner.”

M. Dror Michaelson, MD, PhD, of Massachusetts General Hospital Cancer Center, is the corresponding author for the Journal of Clinical Oncology article.

The study was supported by Pfizer Inc. For full disclosures of the study authors, visit

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