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Brentuximab vedotin improves CTCL outcomes over methotrexate, bexarotene
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SAN DIEGO — Brentuximab vedotin yielded significantly higher response rates and longer PFS than standard-of-care options for cutaneous T-cell lymphoma, according to findings presented at the ASH Annual Meeting and Exposition.
Current systemic therapies for cutaneous T-cell lymphoma (CTCL) — a chronic disease that negatively impacts quality of life and has a poor prognosis when advanced — rarely lead to durable responses, and no therapy has yet to improve outcomes compared with standard of care.
Youn H. Kim, MD, of the division of oncology and department of medicine at Stanford University School of Medicine, and colleague, compared brentuximab vedotin (Adcetris, Seattle Genetics) — a CD30–directed antibody-drug conjugate — with a physician’s choice of methotrexate or bexarotene in a cohort of 131 treatment-experienced patients with CD30-expressing CTCL.
“Brentuximab vedotin has shown significant clinical activity and an acceptable safety profile in CTCL in phase 2 studies,” Kim said.
The intent-to-treat analysis included 128 patients who researchers had randomly assigned to receive 1.8 mg/kg IV brentuximab vedotin once every 3 weeks (n = 64; median age, 62 years) or physicians’ choice (n = 64; median age, 58 years) which consisted of 5 mg to 50 mg oral methotrexate once weekly or 300 mg/m² oral bexarotene once daily for up to 16 3-week cycles. Treatments were administered until disease progression or unacceptable toxicity.
The median number of treatment cycles was 12 (range, 1-16) for brentuximab vedotin compared with 5.5 (range, 1-16) for bexarotene and three (range, 1-16) for methotrexate.
The primary endpoint was ORR lasting 4 months or more (ORR4), which “is a measure of clinically meaningful efficacy that also shows durability of response,” Kim said.
Complete response rate, PFS and symptom burden served as secondary outcome measures.
Median follow-up was 17.5 months.
The primary endpoint rate was 56% for brentuximab vedotin and 13% for physician’s choice (P < .0001). Median PFS was 16.7 months in the brentuximab group and 3.5 months for physician’s choice (HR = 0.27; 95% CI, 0.16–0.43).
More patients assigned brentuximab vedotin than physician’s choice achieved an overall response (67% vs. 20%; P < .0001) or complete response (16% vs. 2%; P = .0046).
“All of the key secondary endpoints were superior in the brentuximab arm,” Kim said. “The response was shown in all clinical stages, including stage IV disease.”
Brentuximab vedotin also bested physician’s choice in terms of Skindex-29 symptom reduction (–27.96 vs. –8.62; P < .0001).
“Overall, in the brentuximab arm, you see superior skin response rates than in the comparator arm,” Kim said.
Grade 3 to grade 4 drug-related adverse events occurred in 29% of patients in both the brentuximab vedotin and physician’s choice groups, whereas grade 3 to grade 4 all-cause events occurred in 41% of patients in the study drug group and 47% of those in the physician’s choice group. Twenty-four percent of patients in the study drug arm discontinued due to adverse events, compared with 8% in the physician’s choice arm.
Two-thirds of patients treated with brentuximab vedotin experienced peripheral neuropathy, which was an “expected” outcome, Kim said. At last follow-up, 82% of those patients experienced an improvement or resolution of this condition.
“This is the first report of a randomized, phase 3 trial in CTCL with convincing demonstration of improved efficacy of a new systemic agent over standard-of-care options,” Kim said. “All endpoints were highly significant. The safety data of brentuximab were consistent with the established tolerability profile. These compelling results have potentially practice-changing implications.” – by Rob Volansky
Reference :
Kim YH, et al. Abstract 182. Presented at: The ASH Annual Meeting and Exposition; Dec. 3-6, 2016; San Diego.
Disclosure: Kim reports board of directors or advisory committee roles with, and research funding from Eisai, Forty Seven Inc, Horizon Pharma, Innate, Kyowa Kirin Pharma, Merck, miRagen, Neumedicine, Portola, Seattle Genetics, Soligenix, Takeda and Tetralogic. Please see the abstract for a list of all other researchers’ relevant financial disclosures.