1. Adding angiogenesis-targeted sunitinib therapy to prednisone in the treatment of metastatic castration-resistant prostate cancer (mCRPC) does significantly improves progression-free survival, but not overall survival.
2. The potential uses of anti-angiogenic therapy in this setting requires further investigation.
Evidence rating level: 1 (Excellent)
Study Rundown: The standard approach to managing metastatic, castration-resistant prostate cancer includes docetaxel-based chemotherapy. However, further malignant progression on this regimen generally leaves only limited options for patients. Previous studies suggest that prostate cancer growth is dependent on angiogenesis, and so sunitinib, a multi-targeted inhibitor of VEGFRs and PDGFRs, may have potential use in this clinical picture. The purpose of this study was to determine whether adding sunitinib to prednisone therapy for men with progressive mCRPC after docetaxel-based chemotherapy improves overall or progression-free survival.
After comparing two treatment arms, one with sunitinib and one with placebo control, the study authors found that adding sunitinib to prednisone did not improve overall survival. However, progression-free survival significantly increased in the treatment arm. Treatment related toxicities included fatigue, asthenia, hand-foot syndrome, and hematologic abnormalities. On the basis of these results, the authors concluded that the potential role of antiangiogenic therapy in mCRPC remains unclear. Though sunitinib improved progression-free survival, it was also associated with significant toxicities. Therefore, choosing between treatment options remains a difficult task for both patients and physicians.
This study benefits from its randomized-controlled design, enrolling large numbers of patients from centers in multiple countries, and use of placebo to test the effects of sunitinib. It should be noted that progression-free survival was a secondary outcome, however.
In-Depth [randomized-controlled trial]: In this double-blinded, placebo-controlled trial of sunitinib therapy, the study authors enrolled patients with pathologically confirmed adenocarcinoma of the prostate that was metastatic and castration-resistant. Patients also had to have failed one previous docetaxel-based regimen. Patients were excluded if they had failed multiple chemotherapy regimens, had experienced brain metastases, significant cardiovascular disease or complications from bone metastases. A total of 873 patients from multiple centers were randomly assigned 2:1 to either oral sunitinib (n = 584) or matched placebo (n = 289) in addition to oral prednisone therapy. The primary end point was overall survival, defined as time from randomization to death. Secondary end points included progression-free survival.
After a median follow-up of 8.7 months, median overall survival was 13.1 months and 11.8 months for sunitinib and placebo, respectively (HR 0.914, 95% CI 0.762-1.097, P = 0.168). Progression-free survival was significantly different between the two arms, median 5.6 versus 4.1 months, (HR 0.725, 95% CI, 0.591-0.89, P < 0.001).
By Monica Parks and Andrew Bishara
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