The European Medicines Agency’s Committee for Medicinal Products for Human Use has recommended approval of brentuximab vedotin (Adcetris) in adults with CD30-positive cutaneous T-cell lymphoma after at least 1 prior systemic therapy.
Julia Scarisbrick, MD
The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended approval of brentuximab vedotin (Adcetris) in adults with CD30-positive cutaneous T-cell lymphoma (CTCL) after at least 1 prior systemic therapy, Takeda Pharmaceuticals, which codevelops the antibody-drug conjugate with Seattle Genetics.
The European Commission will now review the application for its final decision. If approved, brentuximab vedotin would be available for use in the 28-member EU along with Norway, Liechtenstein, and Iceland.
“This opinion represents a crucial first step forward for European patients living with CTCL, a debilitating disease that can have a significant impact on their quality of life,” Julia Scarisbrick, MD, department of dermatology, University Hospital Birmingham, UK, said in a statement. “The results of the ALCANZA trial demonstrate impressive efficacy along with a manageable safety profile when compared with methotrexate and bexarotene, commonly used therapies. If approved in Europe, Adcetris would offer a novel treatment option for CD30-expressing CTCL patients.”
The CHMP reviewed findings from the international, open-label, phase III ALCANZA trial which showed that brentuximab vedotin induced responses lasting at least 4 months in 56.3% of patients versus 12.5% in patients receiving physician’s choice of standard therapies (P <.0001).1,2
ALCANZA 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.
At a median follow-up of 22.9 months, the median 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). 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.
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 ORR4 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 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.