The Role of Sipuleucel-T in Therapy for Castration-Resistant Prostate Cancer: A Critical Analysis of the Literature

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• 作者：Guru Sonpavde^a ; ^b ; ^{guru.sonpavde@usoncology.com} ; Giuseppe Di Lorenzo^c ; Celestia S. Higano^d ; Philip W. Kantoff^e ; Ravi Madan^f ; Neal D. Shore^g
• 关键词：Immunotherapy ; Prostate cancer ; Sipuleucel-T ; CTLA-4 ; PD-1 ; Prostvac VF Tricom ; Ipilimumab
• 刊名：European Urology
• 出版年：2012
• 期刊代码：289_03022838
• 类别：med
• 出版时间：April, 2012
• 卷：61
• 期：4
• 页码：639-647
• 文件大小：741 K

摘要

Context

Sipuleucel-T, an autologous antigen-presenting cell vaccine loaded with prostate acid phosphatase conjugated with granulocyte-macrophage colony-stimulating factor (GM-CSF), yielded a survival advantage in men with metastatic castration-resistant prostate cancer (mCRPC).

Objective

Critically analyze the role of sipuleucel-T in therapy for mCRPC.

Evidence acquisition

A systematic review of the literature was performed in June 2011 using Medline and an abstract search of major cancer conferences. The search strategy included the terms sipuleucel-T, APC-8015, castration-resistant, prostate cancer, and immunotherapy.

Evidence synthesis

The era of targeted immunotherapy was initiated with the regulatory approval in 2010 of sipuleucel-T for asymptomatic and minimally symptomatic mCRPC. The median survival was prolonged by 4.1 mo (25.8 vs 21.7 mo; hazard ratio: 0.78; 95%confidence interval, 0.61-0.98; p = 0.03), coupled with an improvement in 3-yr survival (31.7%vs 23.0%). Outcomes were characterized by the lack of tumor regression or delay in progression. Further development is proceeding in earlier stages of prostate cancer and in the context of a host of emerging agents.

Conclusions

The addition of sipuleucel-T, an immunotherapeutic agent, to the armamentarium represents a paradigm shift in therapy for mCRPC. The rational combination and proper sequencing of sipuleucel-T with other newly approved agents (abiraterone acetate, cabazitaxel) and emerging agents (MDV3100, TAK-700, ipilimumab) will be important to evaluate.