Randomized phase 3 ALCANZA study of brentuximab vedotin vs physician's choice in cutaneous T-cell lymphoma: final data

Abstract

The primary analysis of the phase 3 ALCANZA trial showed significantly improved objective responses lasting ≥4 months (ORR4; primary endpoint) and progression-free survival (PFS) with brentuximab vedotin vs physician's choice (methotrexate or bexarotene) in CD30-expressing mycosis fungoides (MF) or primary cutaneous anaplastic large-cell lymphoma (C-ALCL). Cutaneous T-cell lymphomas often cause pruritus and pain; brentuximab vedotin improved skin symptom burden with no negative effects on quality of life. We report final data from ALCANZA (median follow-up, 45.9 months). Adults with previously treated CD30-expressing MF/C-ALCL were randomly assigned to brentuximab vedotin (n = 64) or physician's choice (n = 64). Final data demonstrated improved responses per independent review facility with brentuximab vedotin vs physician's choice: ORR4; 54.7% vs 12.5% (P < .001); complete response, 17.2% vs 1.6% (P = .002). Median PFS with brentuximab vedotin vs physician's choice was 16.7 months vs 3.5 months (P < .001). Median time to the next treatment was significantly longer with brentuximab vedotin than with physician's choice (14.2 vs 5.6 months; hazard ratio, 0.27; 95% confidence interval, 0.17-0.42; P < .001). Of 44 patients in the brentuximab vedotin arm who experienced any-grade peripheral neuropathy, (grade 3, n = 6; grade 4, n = 0), 86% (38 of 44) had complete resolution (26 of 44) or improvement to grades 1 and 2 (12 of 44). Peripheral neuropathy was ongoing in 18 patients (all grades 1-2). These final analyses confirm improved, clinically meaningful, durable responses and longer PFS with brentuximab vedotin vs physician's choice in CD30-expressing MF or C-ALCL. This trial was registered at https://www.clinicaltrials.gov as #NCT01578499.

Graphical abstract

Figure 1.

PFS per IRF in the ITT population. PFS was defined as the time from randomization until disease progression per IRF or death of any cause, whichever occurred first. Patients who were lost to follow-up, withdrew consent, or discontinued treatment because of undocumented disease progression after the last adequate disease assessment were censored at the last disease assessment.

Figure 2.

PFS per IRF in the ITT population. (A) PFS for patients with MF. (B) PFS for patients with C-ALCL. PFS is defined in Figure 1. Patients were censored at last disease assessment if they withdrew consent, were lost to follow-up, or discontinued treatment because of undocumented disease progression after the last adequate disease assessment.

Figure 3.

TTNT in the ITT population. Time to next antineoplastic therapy was defined as the time from randomization to the date of the first documentation of antineoplastic therapy or the last contact date for subjects who never received antineoplastic therapy. NE, not evaluable.