A subanalysis of the phase 3 clinical trial RESONATE showed that adherence to the recommended dose of ibrutinib in patients with chronic lymphocytic leukemia (CLL) who had received previous therapy improved extended progression-free survival (PFS) compared with patients who did not adhere to the treatment regimen, suggested Paul Barr, MD, Assistant Professor of Medicine and Director of the Clinical Trials Office, Wilmot Cancer Institute, Rochester, NY, who presented the results at ASCO 2015.
The randomized, multicenter, international, head-to-head RESONATE trial included 373 patients with CLL and 18 patients with small lymphocytic leukemia. Patients were randomized to once-daily, 420-mg orally administered ibrutinib, a first-in-class inhibitor of Bruton’s tyrosine kinase inhibitor, or to intravenous ofatumumab, a CD20 antigen inhibitor. The most common nonhematologic adverse events observed in patients who received ibrutinib included diarrhea, fatigue, pyrexia, and nausea.
The goal of this subanalysis of RESONATE was to investigate the impact of adhering to the recommended dose of ibrutinib in patients with CLL. A total of 195 patients with previously treated CLL received 420 mg of ibrutinib for 8.3 months. At the end of the treatment period, the mean dose intensity—defined as the proportion of actually used doses versus planned doses of ibrutinib 420 mg—was 95%. Overall, the majority of dose interruptions reinstated the 420 dose after the dose reduction: 3.6% of the patients had 1 dose reduction and 0.5% had 2 dose reductions because of adverse events.
The PFS duration was longer among patients who used the recommended 420-mg dose of ibrutinib (median not yet reached at the time of the analysis) compared with 11 months for the patients who took lower doses. This had no relation to high-risk factors in this patient population (such as deletion 17p or p53 mutation).
Furthermore, patients who missed the recommended ibrutinib dose for ≥8 consecutive days had significantly more adverse events compared with patients who adhered to the recommended 420-mg dose (33% vs 13%, respectively).
“These data show that when patients take Imbruvica daily, at the recommended dose, it can improve their chance of achieving a sustained treatment response and delay disease progression,” Dr Barr said. “As clinicians, it is important that we ensure that patients take this once-daily, oral medication as recommended in order to achieve the best possible outcome in treating their cancer.”