“In three years, four drugs have gained regulatory approval for the treatment of metastatic and unresectable melanoma, with at least seven other drugs having recently completed, currently in, or soon to be in phase III clinical testing. This amazing achievement has been made following a remarkable increase of knowledge in molecular biology and immunology that led to the identification of high-valued therapeutic targets and the clinical development of agents that effectively engage and inhibit these targets. The discovery of either effective molecularly targeted therapies or immunotherapies would have led to dramatic improvements to the standard-of-care treatment of melanoma. However, through parallel efforts that have showcased the efficacy of small-molecule BRAF and MAP–ERK kinase (MEK) inhibitors, as well as the immune checkpoint inhibitors, namely ipilimumab and the anti-PD1/PDL1 antibodies (lambrolizumab, nivolumab, MPDL3280), an opportunity exists to transform the treatment of melanoma specifically and cancer generally by exploring rational combinations of molecularly targeted therapies, immunotherapies, and molecular targeted therapies with immunotherapies. This overview presents the historical context to this therapeutic revolution, reviews the benefits and limitations of current therapies, and provides a look ahead at where the field is headed.”
People with melanomas that have spread can live as long as a decade when treated with the U.S Food and Drug Administration (FDA)-approved immunotherapy drug Yervoy (ipilimumab), according to a report at a cancer conference in Amsterdam, Netherlands. Ipilimumab activates the immune system’s attack on tumor cells, which is normally inhibited. The researchers evaluated 12 ipilimumab trials totaling more than 1,800 people with melanoma, making this the largest follow-up skin cancer study ever. They found that 22% survived at 3 years and 17% survived at 7 years and were still alive at up to 10 years. Now, Yervoy manufacturer Bristol-Myers is testing the combination of ipilimumab with an experimental immunotherapy drug called nivolumab, which blocks a protein (PD-1) that lets tumor cells evade the immune system. So far, the combo treatment outperforms ipilimumab alone in an early trial, extending life to a year in 82% of 53 people with melanoma.
A clinical trial examining a new lung cancer drug is enrolling participants at numerous locations throughout the U.S. BMS-936558 (nivolumab) targets PD-1, a protein on the surface of immune cells that suppresses the immune response. By inhibiting PD-1, nivolumab ‘unleashes’ the immune system so it can continue its attack on tumors. The trial will investigate whether patients with advanced squamous cell carcinoma (SCC) of the lung, a type of non-small cell lung cancer (NSCLC), do better when treated with either nivolumab or the chemotherapy agent docetaxel (Taxotere). To find out more, call 855-216-0126 or visit the trial’s website.
Following in the footsteps of positive results for the drug nivolumab, another anti-PD1 antibody, lambrolizumab (formerly MK-3475), is also showing promising activity in melanoma. At the annual meeting of the American Society of Clinical Oncology, Antoni Ribas, MD, PhD, of the Jonsson Comprehensive Cancer Center at the University of California, Los Angeles, presented data from a large, 1,000-plus patient phase I trial that also included other cancer types. Continue reading…
Preliminary results from an ongoing early clinical trial of the new lung cancer drug nivolumab show that the treatment is tolerable. Out of 43 patients with advanced non-small cell lung cancer (NSCLC) treated with nivolumab and chemotherapy, slightly less than half experienced serious side effects. In most cases, these side effects were manageable with medication and/or discontinuation of nivolumab. Nivolumab targets PD-1, a protein on the surface of immune cells that switches off the immune response when it binds to another protein, PD-L1, which is often expressed on tumors. By inhibiting PD-1, nivolumab enables the immune system to continue attacking cancer cells. Additional clinical trials focusing on patients with squamous or non-squamous NSCLC will investigate whether nivolumab is more effective than the chemotherapy drug docetaxel (Taxotere).
An experimental immunotherapy drug called nivolumab may increase survival in people with melanomas that have spread. Nivolumab blocks a protein called PD-1, which lets tumor cells evade the immune system. In a phase I trial of melanoma patients who had not responded to previous treatments, researchers found tumors shrank in 41% of those given the highest dose of nivolumab (3 mg/kg). Overall, 62% survived to 1 year and 43% survived to 2 years and only 2% had severe side effects. Nivolumab is currently being tested in three phase III trials. These findings were among several advances in immunotherapy treatments for melanoma presented at the American Society of Clinical Oncology’s 2013 meeting.
“In patients with melanoma, ipilimumab (an antibody against cytotoxic T-lymphocyte–associated antigen 4 [CTLA-4]) prolongs overall survival, and nivolumab (an antibody against the programmed death 1 [PD-1] receptor) produced durable tumor regression in a phase 1 trial. On the basis of their distinct immunologic mechanisms of action and supportive preclinical data, we conducted a phase 1 trial of nivolumab combined with ipilimumab in patients with advanced melanoma.”
A promising new therapy for the most common form of lung cancer appears to produce largely manageable side effects, and an ongoing clinical trial is determining whether the compound treats tumors more effectively than what’s on market…