Ipilimumab Fails to Significantly Prolong Survival in Patients With Advanced Prostate Cancer

“Bristol-Myers Squibb Company, the manufacturer of ipilimumab (Yervoy), released results from its phase III randomized double-blind study investigating the drug in men with metastatic castration-resistant prostate cancer. The study findings show that ipilimumab, a monoclonal antibody that blocks the action of CTLA-4, failed to meet its primary endpoint of prolonging overall survival. However, antitumor activity was observed in other endpoints, including progression-free survival. Also, a subgroup analysis suggests that patients with less advanced disease may experience the most benefit from ipilimumab. The full results of the study will be presented at the 2013 European Cancer Congress on September 28, 2013.”


Bristol's Yervoy Falls Short in Prostate Cancer Study

“Bristol-Myers Squibb Co’s immunotherapy drug Yervoy failed to significantly prolong survival among patients with advanced prostate cancer who had previously received chemotherapy, according to limited data from the first late-stage study of the drug for the condition. Yervoy (ipilimumab) frees the immune system to attack and kill cancer cells by blocking the action of a protein called CTLA-4. The closely followed drug was approved in 2011 to treat melanoma, the most deadly form of skin cancer, and is well on its way to achieving annual blockbuster sales of $1 billion.”


Bristol's Yervoy Falls Short in Prostate Cancer Study

“Bristol-Myers Squibb Co’s immunotherapy drug Yervoy failed to significantly prolong survival among patients with advanced prostate cancer who had previously received chemotherapy, according to limited data from the first late-stage study of the drug for the condition. Yervoy (ipilimumab) frees the immune system to attack and kill cancer cells by blocking the action of a protein called CTLA-4. The closely followed drug was approved in 2011 to treat melanoma, the most deadly form of skin cancer, and is well on its way to achieving annual blockbuster sales of $1 billion.”


Clinical Activity of Ipilimumab for Metastatic Uveal Melanoma: A Retrospective Review of the Dana-Farber Cancer Institute, Massachusetts General Hospital, Memorial Sloan-Kettering Cancer Center, an…

“Background: Uveal melanoma exhibits a high incidence of metastases; and, to date, there is no systemic therapy that clearly improves outcomes. The anticytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4) antibody ipilimumab is a standard of care for metastatic melanoma; however, the clinical activity of CTLA-4 inhibition in patients with metastatic uveal melanoma is poorly defined. Methods: To assess ipilimumab in this setting, the authors performed a multicenter, retrospective analysis of 4 hospitals in the United States and Europe. Clinical characteristics, toxicities, and radiographic disease burden, as determined by central, blinded radiology review, were evaluated…Conclusions: In this multicenter, retrospective analysis of 4 hospitals in the United States and Europe of patients with uveal melanoma, durable responses to ipilimumab and manageable toxicity were observed. Cancer 2013. © 2013 American Cancer Society.”


Checkpoint Modulation in Melanoma: An Update on Ipilimumab and Future Directions

“Ipilimumab, an anti-cytotoxic T-lymphocyte antigen 4 antibody, was the first therapy demonstrated to improve overall survival in melanoma. Since ipilimumab’s approval by the FDA in 2011, a wealth of data has amassed, helping clinicians to optimize its use. We have learned how to mitigate the adverse effects of ipilimumab, identified its effects in melanoma subpopulations such as those with brain metastases, uveal melanoma, and mucosal melanoma, discovered potential biomarkers of activity, and investigated its use in combination with other therapeutic modalities. These discoveries have paved the way for rapid development of second-generation immunomodulatory antibodies such as inhibitors of the programmed cell death 1 receptor axis. These new agents hold promise as monotherapy, but perhaps the greatest allure lies in the possibility of combining these agents in synergistic multidrug regimens.”


Molecular Pathways: Co-Expression of Immune Checkpoint Molecules: Signaling Pathways and Implications for Cancer Immunotherapy

“The expression of immune checkpoint molecules on T cells represents an important mechanism that the immune system uses to regulate responses to self-proteins. Checkpoint molecules include CTLA-4 (Cytotoxic T Lymphocyte Antigen-4), PD-1 (Programmed Death-1), LAG-3 (Lymphocyte Activation Gene-3), TIM-3 (T cell Immunoglobulin and Mucin protein-3) and several others. Previous studies have identified individual roles for each of these molecules, but more recent data show that co-expression of checkpoint molecules occurs frequently on cancer-specific T cells, as well as on pathogen-specific T cells in chronic infections. While the signaling pathways associated with each checkpoint molecule have not been fully elucidated, blocking multiple checkpoints with specific monoclonal antibodies results in improved outcomes in several chronic viral infections as well as in a wide array of pre-clinical models of cancer. Recent clinical data suggest similar effects in patients with metastatic melanoma. These findings support the concept that individual immune checkpoint molecules may function through non-overlapping molecular mechanisms. Here we review current data regarding immune checkpoint molecule signaling and co-expression, both in cancer and infectious disease, as well as the results of preclinical and clinical manipulations of checkpoint proteins.”


Controlled Local Delivery of CTLA-4 Blocking Antibody Induces CD8+ T-Cell–Dependent Tumor Eradication and Decreases Risk of Toxic Side Effects

“Blockade of CTLA-4 by antibodies has potentiated antitumor T-cell responses in both preclinical models and clinical trials. However, treatment with CTLA-4 blocking antibodies is associated with autoimmune and inflammatory side effects. In this study, we propose a novel administration method for CTLA-4 blocking antibodies as monotherapy.”


Controlled Local Delivery of CTLA-4 Blocking Antibody Induces CD8+ T-Cell–Dependent Tumor Eradication and Decreases Risk of Toxic Side Effects

“Blockade of CTLA-4 by antibodies has potentiated antitumor T-cell responses in both preclinical models and clinical trials. However, treatment with CTLA-4 blocking antibodies is associated with autoimmune and inflammatory side effects. In this study, we propose a novel administration method for CTLA-4 blocking antibodies as monotherapy.”


Controlled Local Delivery of CTLA-4 Blocking Antibody Induces CD8+ T-Cell–Dependent Tumor Eradication and Decreases Risk of Toxic Side Effects

“Blockade of CTLA-4 by antibodies has potentiated antitumor T-cell responses in both preclinical models and clinical trials. However, treatment with CTLA-4 blocking antibodies is associated with autoimmune and inflammatory side effects. In this study, we propose a novel administration method for CTLA-4 blocking antibodies as monotherapy.”