Five years after its debut, ipilimumab (Yervoy) has revolutionized the treatment of patients with metastatic melanoma and ushered in the era of immune checkpoint inhibitors into anticancer therapies.
Now, however, the CTLA-4 inhibitor has been eclipsed by anti-PD-1 antibodies, which are approved not only in melanoma but also in non–small cell lung cancer (NSCLC) and renal cell carcinoma (RCC). Although ipilimumab continues to demonstrate strikingly durable responses in melanoma, some lasting up to a decade, these occur in the minority of patients and a frustrating dearth of predictive biomarkers makes it hard to pick those patients out from the crowd.
Nevertheless, new research is carving out a role for ipilimumab and a second CTLA-4-targeting drug, tremelimumab, as combination therapy with potential in a variety of solid tumors. In addition to combinations with other immune checkpoint inhibitors, the agents are being evaluated across a breadth of other strategies, including in combination with conventional cytotoxic therapies, targeted therapies, and other types of immunotherapy (Table).
CTLA-4 is among many immune system regulators with cellular effects. Stimulatory effects are depicted with green arrows, and inhibitory effects are depicted with red symbols. PD-1, KIR, LAG-3, GITR, and TIM-3 are immune checkpoints.
DC indicates dendritic cell; MHC, major histocompatibility complex; NK, natural killer; TCR, T-cell receptor; T REG, regulatory T cell.
Patel MA, Kim JE, Ruzevick J, Lim M. Present and future of immune checkpoint blockade: monotherapy to adjuvant approaches. World J Immunol. 2015;5(1):1-15. Reprinted with permission.
|Title||Expiration Date||CME Credits|
|34th Annual Miami Breast Cancer Conference® Clinical Case Vignette Series™||May 25, 2018||2.0|
|Community Practice Connections™: CDK4/6 Inhibitors With the Experts: The Role of Emerging Agents for the Management of Metastatic Breast Cancer||May 30, 2018||2.0|