Brentuximab Vedotin Approved in Europe for CTCL

Julia Scarisbrick, MD

Brentuximab vedotin (Adcetris) has been approved by the European Commission for the treatment of patients with CD30-positive cutaneous T-cell lymphoma (CTCL) after at least 1 prior systemic therapy.

The approval of the antibody-drug conjugate is based on results from the phase III ALCANZA trial, in which brentuximab vedotin induced responses lasting at least 4 months in 56.3% of patients compared with 12.5% in patients receiving physician’s choice of standard therapies (P <.0001).^1,2

The approval follows the recommendation of the European Medicines Agency’s Committee for Medicinal Products for Human Use. Takeda Pharmaceuticals issued a press release announcing that brentuximab is now available in the 28 member states of the European Union, Norway, Liechtenstein and Iceland.

“CTCL is a subtype of non-Hodgkin lymphoma that primarily involves the skin; it typically presents with red, scaly patches or thickened plaques of skin that often mimics eczema or psoriasis and can have a substantial impact on patients’ self-esteem. There are few approved CTCL treatment options with only limited efficacy, creating a significant unmet need for these patients,” Julia Scarisbrick, MD, Department of Dermatology, University Hospital Birmingham, said in a statement.

“The approval of Adcetris in this setting brings a much needed, effective treatment option to patients living with CTCL and I am looking forward to be able to offer this treatment to CD30-positive patients who have received one prior systemic therapy,” added Scarisbrick, who was a member of the research team investigating brentuximab for this indication.

The international, open-label ALCANZA trial included 131 patients with CD30-expressing (≥10% of infiltrate by central review) mycosis fungoides (MF) or primary cutaneous anaplastic large cell lymphoma (pcALCL), the 2 most common subtypes of CTCL. The intent-to-treat population comprised 128 patients, 97 with MF and 31 with pcALCL. Three patients were excluded because their level of CD30 expression was too low.

Patients with MF had to have received at least 1 prior systemic therapy and those with pcALCL were required to have prior radiation therapy or at least 1 systemic therapy.

Patients were randomly assigned to brentuximab vedotin (n = 64) or physician’s choice of the standard treatments methotrexate or bexarotene (n = 64). Brentuximab vedotin was administered intravenously at 1.8 mg/kg once every 3 weeks for up to 48 weeks (16 cycles). Methotrexate was dosed at 5 to 50 mg once weekly and bexarotene was administered orally at 300 mg/m² once daily. Treatments were administered until disease progression or unacceptable toxicity.

The objective response rate (ORR) was 67% versus 20% (P <.0001), with complete response (CR) rates of 16% versus 2% (P = .0046), in the brentuximab vedotin and control arms, respectively. The median progression-free survival (PFS) was 16.7 months with brentuximab vedotin versus 3.5 months with physician’s choice (hazard ratio, 0.270; 95% CI, 0.169-0.430; P <.0001).

Symptom reduction, as measured by Skindex-29, was significantly better with brentuximab vedotin versus physician’s choice (-27.96 vs -8.62; P <.0001).

ORR was 50% Among patients with MF who received brentuximab vedotin versus 10% with physician’s choice. The ORR and CR rates were 65% versus 16% and 10% versus 0, respectively. In patients with pcALCL who received brentuximab vedotin, the ORR was 75% versus 20% with physician’s choice. The ORR and CR rates were 75% versus 33% and 31% versus 7%, respectively.

In patients with pcALCL in the skin only who received brentuximab vedotin, the ORR4 was 89% versus 27% with physician’s choice. The ORR and CR rates were 89% versus 45% and 44% versus 9%, respectively. Among pcALCL patients with extracutaneous disease who received brentuximab vedotin, the ORR4 was 57% versus 0 with physician’s choice. The ORR and CR rates were 57% versus 0 and 14% versus 0, respectively.

Patients assigned to brentuximab vedotin were less likely to experience grade ≥3 adverse events (AEs), 41% versus 47%. Patients in both arms were equally likely to experience serious AEs (29%).

Two-thirds of patients in the brentuximab vedotin arm experienced peripheral neuropathy (9%, grade 3) versus 6% in the control arm. Other common all-grade AEs included nausea (36% vs 13%), diarrhea (29% vs 6%), fatigue (29% vs 27%), vomiting (17% vs 5%), alopecia (15% vs 3%), pruritus (17% vs 13%), pyrexia (17% vs 18%), decreased appetite (15% vs 5%), and hypertriglyceridemia (2% vs 18%).

AE-related discontinuations occurred in 24% of patients in the brentuximab vedotin arm and 8% of patients in the physician’s choice arm. There were 4 patient deaths in the brentuximab vedotin arm, 3 of which were considered unrelated to treatment. No patients died on-study in the control arm.

References

1. Kim YH, Whittaker S, Horwitz SM, et al. Brentuximab vedotin demonstrates significantly superior clinical outcomes in patients with CD30-expressing cutaneous T cell lymphoma versus physician's choice (methotrexate or bexarotene): the phase 3 ALCANZA study. Presented at: 58th Annual ASH Annual Meeting; December 3-6, 2016; San Diego, CA. Abstract 182.
2. Prince HM, Kim YH, Horwitz SM, et al. Brentuximab vedotin or physician's choice in CD30-positive cutaneous T-cell lymphoma (ALCANZA): an international, open-label, randomised, phase 3, multicentre trial [published online June 6, 2017]. Lancet. 2017 doi: 10.1016/S0140-6736(17)31266-7.