ASCO 2013: New Drug Targeting PI3K-delta Shows Strong Activity in Early Trial for High-risk Chronic Lymphocytic Leukemia
Results from a phase I study of a new oral targeted drug, idelalisib (GS-1101), show the agent has potential as a therapy for relapsed or treatment-resistant chronic lymphocytic leukemia (CLL). The drug produced rapid and long-lasting tumor shrinkage in half of the patients treated with single-agent therapy, stalling disease progression for 17 months, on average. The activity of the drug is noteworthy, given that the patients had already undergone an average of five prior therapies. The results will be presented at the 2013 ASCO Annual Meeting in Chicago (Abstract 7003).
CLL, which is typically diagnosed through a routine blood test, is a slow-growing cancer, and many patients do not require treatment until they start having symptoms. The vast majority of patients with CLL experience a relapse at some point after initial treatment with chemoimmunotherapy, and about 20% of patients have refractory disease. Both of those categories of patients are in need of better treatments, as the currently approved options (immunotherapy and chemotherapy) have limited success.
PI3K Inhibitors
Idelalisib is the first drug that selectively blocks PI3K-delta, a subtype of PI3K proteins that is overactive specifically in B-cell lymphoma, and is critical for tumor growth. While other PI3K inhibitors have been explored, this is the first study of a PI3K inhibitor—including a PI3K-delta inhibitor—specifically in patients with CLL.
“We are reaching a point in CLL where we have multiple agents in development that are very effective. Drugs like idelalisib are probably going to change the landscape of the disease in the next few years,” said lead study author Jennifer Brown, MD, PhD, an Assistant Professor of Medicine at Dana-Farber Cancer Institute. “While this research is still early and ongoing, we hope this drug, along with others like it, will lead to prolonged survival and eventually help turn CLL into a condition that is treated like high blood pressure, where a patient can take a couple of pills every day. In the shorter term, these drugs may also provide an alternative to chemotherapy in elderly patients who tend not to tolerate chemotherapy well.”
Study Details
This trial included 54 patients with refractory or relapsed CLL who received idelalisib. The patients’ cancer had worsened despite having received a median of five prior therapies. The average duration of idelalisib treatment was 9 months. Tumor reduction with clinical benefit was rapid for this disease, generally occurring in the first 2 months after beginning therapy, and was observed in about two-thirds of patients. On average, the drug delayed disease progression by 17 months, which is better than typically expected for a sixth-line therapy, which might usually have benefit for 6 to 12 months. Many patients experienced a decrease in disease symptoms, such as fatigue. Patients who benefited from the drug were offered the opportunity to continue treatment on an extension study.
The researchers reported that side effects were manageable; only 7% of patients discontinued treatment due to treatment-related effects.
“This study illustrates how our growing understanding of tumor biology enables development of highly active and highly promising targeted drugs. It also offers a glimpse at the possibility of a new, chemotherapy-free alternative for chronic blood cancers, where active treatment is simple, effective, and may even improve a patient’s overall quality of life,” said ASCO President Sandra M. Swain, MD, FACP.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
