In a phase I study, Gilead Sciences' PI3K-δ inhibitor idelalisib produced rapid tumor shrinkage—a response that lasted for 17 months on average—in about half of the 54 patients with chronic lymphocytic leukemia who participated.

In a phase I study, Gilead Sciences' targeted agent idelalisib (GS-1101) demonstrated potential for treating relapsed or treatment-resistant chronic lymphocytic leukemia (CLL). Half of the 54 patients in the study experienced rapid tumor shrinkage that lasted for 17 months on average.

The drug's activity was particularly noteworthy given that the patients had already been treated with an average of 5 other therapies, noted the study's first author, Jennifer Brown, MD, PhD, an assistant professor of medicine at Dana-Farber Cancer Institute in Boston, MA. Brown presented the findings at a May 15 press conference for the American Society for Clinical Oncology's (ASCO) 2013 Annual Meeting in Chicago, IL, May 31–June 4.

New, more effective treatments are needed for CLL, a B-cell malignancy, because the vast majority of patients will experience a relapse at some point. In addition, about 20% of patients have refractory disease, meaning that they relapse within 6 months of their initial treatment or do not respond to treatment at all. Successive treatments usually can't keep the disease in check for long.

Idelalisib selectively blocks PI3K-δ, an isoform of PI3K that is overactive in many B-cell malignancies, thus reducing tumor cell proliferation and enhancing apoptosis.

Patients in the trial took doses of idelalisib ranging from 50 to 350 mg twice a day for up to 48 weeks. (Those who continued to respond to the drug could continue to take it by enrolling in an extension study, and 23 patients did so.) In general, the drug was well tolerated, Brown said, noting that adverse effects included elevated liver enzymes, diarrhea, and rash. Only 7% of patients discontinued treatment due to side effects.

The overall response rate was 56%, with 2 patients experiencing a complete response and 28 experiencing a partial response. Tumor reduction happened quickly, generally occurring during the first 2 months of treatment.

“The substantial clinical activity of idelalisib that we observed justifies further clinical development in CLL,” Brown said. The drug is being tested in combination with other agents in other blood cancers.

Given how heavily the patients had been pretreated, the average progression-free survival time of 17 months was “pretty incredible,” commented Sandra Swain, MD, president of ASCO and medical director at Washington Cancer Institute at MedStar Washington Hospital Center in Washington, DC. Researchers noted that they would typically expect such patients to benefit for about 6 to 12 months with a new treatment.

“This is really another exciting discovery and success in precision medicine,” said Swain, adding that many CLL patients are older than 70 and often don't tolerate chemotherapy well. “This study demonstrates that we may soon have a new alternative to chemotherapy for slow-growing blood cancers and a simpler treatment—this is an oral treatment—to improve patients' quality of life.”