Adding the targeted drug Imbruvica (ibrutinib) to a standard combination treatment reduced the risk of disease progression by 80 percent compared with the standard combination alone in patients with pretreated chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), according to results from the phase 3 HELIOS study.
Imbruvica prevents new cancer cells from growing by inhibiting the activity of the enzyme Bruton’s tyrosine kinase (BTK). In the study, it was added to the standard pairing of the chemotherapy Treanda (bendamustine) and Rituxan (rituximab), which recognizes the protein CD20 on the outsides of cancerous B cells and helps the immune system to kill them.
The significant progression-free survival (PFS) benefit of the triplet combination was determined during an interim analysis in March 2015, at which point the study was unblinded and patients receiving placebo were allowed to cross over to the Imbruvica arm.
The results were announced May 30 during the 2015 annual meeting of the American Society of Clinical Oncology (ASCO), a gathering of nearly 30,000 oncology professionals in Chicago.
“This becomes one of the most important changing points in the history of CLL, where the treatment of CLL patients will no longer be BR (bendamustine/rituximab), but BR with ibrutinib,” lead study author Asher Chanan-Khan, a professor of Medicine at Mayo Clinic, said when presenting the HELIOS data during a press briefing during the ASCO meeting.
The double-blind, phase 3 HELIOS trial randomized 578 previously treated patients with measurable relapsed/refractory CLL/SLL to BR for a maximum of six cycles plus either placebo (n = 289) or 420 mg/day of Imbruvica (n = 289). The full six cycles of BR were completed by 83 percent and 78 percent of patients in the Imbruvica and placebo arms, respectively.
The median patient age was 64 years, and patients had received an average of two prior therapies. Patients with 17p deletions, a chromosomal glitch, affecting more than 20 percent of cells were not included in the study.
The study was powered to detect a hazard ratio (HR) of 0.70 with a P value of .025 for significance. PFS was the primary outcome measure, with secondary endpoints focused on overall survival (OS) and objective response rate (ORR).
The interim analysis was conducted following 50 percent of events. At the time of the review, 31 percent (n = 90) of patients had progressed on placebo and crossed over to the Imbruvica arm, as allowed by the study design.
At a median follow-up of 17.2 months, PFS with Imbruvica was not yet reached, as compared with 13.3 months for patients receiving BR alone (HR = 0.203; 95% confidence interval [CI], 0.150-0.276; P <.0001). The PFS benefit held up across subgroups of high-risk patients.
Commenting on the PFS data, Chanan-Khan said, “You cannot get a better hazard ratio than this. It brings a lot of joy to see such an impactful therapy altering the course of the disease so early…The [PFS] curves started to differentiate four months into analysis, and that is a great testament of how soon the impact of this regimen was.”
ORR was 82.7 percent in the Imbruvica arm versus 67.8 percent in the control group (P <.0001). Complete response (CR) rates (including CR with incomplete blood count recovery) were 10.4 percent versus 2.8 percent with Imbruvica versus placebo, respectively.