ASH 2017: ALCANZA Trial: Brentuximab Vedotin in CD30-Expressing Cutaneous T-Cell Lymphoma
Updated results from the phase III ALCANZA clinical trial evaluating brentuximab vedotin (Adcetris) in CD30-expressing cutaneous T-cell lymphoma (CTCL) were presented by Horwitz et al at the 59th American Society of Hematology (ASH) Annual Meeting & Exposition (Abstract 1509). The presentation highlighted longer-term durability data from the trial of single-agent brentuximab vedotin for the treatment of patients with primary cutaneous anaplastic large cell lymphoma (ALCL) or CD30-expressing mycosis fungoides. Together, these comprise approximately 70% of CTCL diagnoses and the majority of patients who require systemic therapy.
Information on ALCANZA
ALCANZA was a randomized, open-label phase III study designed to evaluate single-agent brentuximab vedotin vs a control arm of investigator’s choice of standard of care therapies—methotrexate or bexarotene—in patients with CD30-expressing primary cutaneous ALCL or mycosis fungoides. Patients with primary cutaneous ALCL must have received at least one prior systemic or radiation therapy and patients with MF must have received at least one prior systemic therapy. A total of 131 patients were randomized, with 128 patients in the intent-to-treat population. Sixty-four patients were assigned to the brentuximab vedotin arm and 64 patients were assigned to the control arm. Patients received brentuximab vedotin or investigator’s choice of methotrexate or bexarotene for up to approximately 1 year.
Data from longer-term patient follow-up per investigator assessment in the phase III ALCANZA trial after a median observation time of 33.9 months from the first dose of brentuximab vedotin vs physician’s choice include:
- The trial achieved its primary endpoint of demonstrating a highly statistically significant improvement in the rate of objective response lasting at least 4 months (per investigator assessment) in the brentuximab vedotin arm vs the control arm: 60.9% in the brentuximab vedotin arm compared to 7.8% in the control arm (P < .001).
The key secondary endpoints per investigator, including complete response rate, progression-free survival, and reduction in the burden of symptoms during treatment (per Skindex-29 questionnaire), continued to be all highly statistically significant in favor of the brentuximab vedotin arm.
- The median progression-free survival per investigator in the brentuximab vedotin arm was 15.8 months, compared to 3.6 months in the control arm (hazard ratio [HR] = 0.373; 95% confidence interval [CI] = 0.245–0.569; P < .001).
- The complete response rate in the brentuximab vedotin arm was 18.8%, compared to 0% in the control arm (P < .001).
- Patient-reported quality of life assessed by the Skindex-29 questionnaire showed significantly greater symptom reduction for patients in the brentuximab vedotin arm vs the control arm (mean maximum change of –28.08 vs –8.62; P < .001).
At the time of the analyses, 47 patients (73%) in the brentuximab vedotin arm and 48 patients (75%) in the physician’s-choice arm had received one or more subsequent skin-directed or systemic therapy. The median time to next treatment in the brentuximab vedotin arm was significantly longer at 14.2 months compared with the physician’s-choice arm at 6.1 months (P < .001). In the brentuximab vedotin vs physician’s-choice arms, the probability of patients not requiring subsequent skin-directed or systemic therapy was greater at 1 year (65.5% vs 15.3%) and 2 years (24.6% vs 4.4%).
Peripheral neuropathy events were observed in 44 (67%) of 66 patients in the brentuximab vedotin arm and 4 (6%) of 62 patients in the physician’s-choice arm. In the brentuximab vedotin arm, 86% of patients reported resolution or improvement in peripheral neuropathy events, with 59% reporting resolution of all events after a median of 30 weeks and 27% reporting some improvement after a median of 13 weeks. Eighteen patients had ongoing peripheral neuropathy events, including 15 patients with grade 1 events and 3 patients with grade 2 events.
In November 2017, the U.S. Food and Drug Administration approved brentuximab vedotin for the treatment of adult patients with primary cutaneous ALCL or CD30-expressing mycosis fungoides who have received prior systemic therapy based on the results of the phase III ALCANZA clinical trial.
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®.
