Abstract
Compared with a physician's choice of either methotrexate or bexarotene, the CD30-directed antibody–drug conjugate brentuximab vedotin led to significantly superior clinical responses in patients with cutaneous T-cell lymphomas, according to the results of the international phase III ALCANZA trial.
Treatment with the antibody–drug conjugate brentuximab vedotin (Adcetris; Seattle Genetics) leads to significantly superior responses in patients with CD30-expressing cutaneous T-cell lymphomas (CTCL) compared with a physician's choice of two common therapies. That's the conclusion of the phase III ALCANZA study, which was presented last month at the annual meeting of the American Society of Hematology in San Diego, CA.
No systemic therapy for CTCL, a chronic disease with an often poor prognosis, has been shown to be more effective than standard therapies. However, two previous phase II, single-arm studies of brentuximab vedotin found marked activity against CTCL, prompting investigators to launch the randomized, open-label, international ALCANZA trial for previously treated patients with CD30-expressing tumors.
Investigators enrolled 128 patients with mycosis fungoides and primary cutaneous anaplastic large cell lymphoma, two subtypes of CTCL. In order to qualify for the trial, at least 10% of a patient's tumor cells had to express CD30. Half of the patients received brentuximab vedotin, and the rest received their physician's choice of either methotrexate or bexarotene, two therapies commonly prescribed around the world for CTCL. The trial's primary endpoint was ORR4, which accounts for the overall response rate (ORR) as well as the duration of the response, which had to be at least 4 months.
After a median follow-up period of 17.5 months, the ORR4 strongly favored brentuximab vedotin over the physician's choice therapies, 56% vs. 13%, respectively, as did median progression-free survival, 16.7 months vs. 3.5 months, reported Youn Kim, MD, of Stanford University School of Medicine in Palo Alto, CA, the study's lead author. Traditionally measured ORR was 67% for the brentuximab vedotin group compared with 20% for the physician's choice group.
Serious adverse events occurred in 29% of patients in each group, Kim noted. However, peripheral neuropathy affected 67% of those who received brentuximab vedotin, compared with 6% of those who received methotrexate or bexarotene. For most patients, the peripheral neuropathy improved or had stopped by their last follow-up appointment. More patients in the brentuximab vedotin group discontinued treatment than in the physician's choice group—24% vs. 8%. Four patients taking brentuximab vedotin died within 30 days of taking their last dose, but three of the deaths were deemed unrelated to the drug. On the plus side, the itching and skin infections that accompany CTCL were significantly reduced with brentuximab vedotin, bettering patients' quality of life.
“These compelling results have potential practice-changing implications for the use of brentuximab vedotin in managing CD30-expressing CTCL in patients who require systemic therapy,” said Kim.
Asked about the minimum of 10% CD30 expression required for trial enrollment, Kim said that about half of all patients with CTCL meet this threshold. However, she stressed that future trials could be designed to include patients with lower expression levels. Patients' tumors are heterogeneous, she explained, “so depending upon which lesion you biopsy, you could have 10% or less,” which might account for positive responses among such patients in other trials. –Suzanne Rose