Brentuximab vedotin (BV) induces significantly superior clinical outcomes in patients with CD30-expressing cutaneous T-cell lymphoma (CTCL) as compared with physician's choice with methotrexate or bexarotene, according to a new study presented at the American Society of Hematology Annual Meeting & Exposition, held December 3–6, 2016.
SAN DIEGO-Brentuximab vedotin (BV) induces significantly superior clinical outcomes in patients with CD30-expressing cutaneous T-cell lymphoma (CTCL) as compared with physician's choice with methotrexate or bexarotene, according to a new study presented (abstract 182) at the American Society of Hematology Annual Meeting & Exposition, held December 3–6, 2016.
“This is the first report of a randomized phase III trial in CTCL with convincing demonstration of improved efficacy of a new systemic agent over standard-of-care options. BV showed superior primary and secondary efficacy outcomes over methotrexate or bexarotene in mycosis fungoides (MF) and primary cutaneous anaplastic large cell lymphoma (pcALCL). These compelling results have potential practice-changing implications for the use of BV in managing CD-30 expressing CTCL in patients who require systemic therapy,” said lead author Youn H. Kim, MD, an oncologist at Stanford University School of Medicine, Stanford, Calif.
The CD30-directed antibody-drug conjugate BV has demonstrated marked clinical activity in two phase II single-arm trials in CTCL. These results led to a randomized, open-label, multicenter, phase III trial of the efficacy and safety of the drug as compared to physician's choice of methotrexate or bexarotene in 128 previously treated patients with CD30-expressing CTCL.
The MF patients had received one or more prior systemic therapies and the pcALCL patients had received one or more prior systemic therapies or radiotherapy. The patients were randomized to receive BV 1.8 mg/kg IV once every 3 weeks (64 patients) or either methotrexate 5–50 mg orally once weekly or bexarotene 300 mg/m² orally once daily (64 patients) for up to 16 three-week cycles, until disease progression or unacceptable toxicity.
The primary endpoint was ORR lasting 4 or more months (ORR4), an endpoint that captures response rate and duration as a single measurement. “After discussing with experts and the FDA [US Food and Drug Administration], we decided that ORR does not capture meaningful responses. Even complete responses in CTCL are of short duration and not meaningful,” said Kim.
Baseline characteristics of the patients were generally balanced between arms, with the exception of more patients with extracutaneous disease in the BV arm.
At a median follow-up of 17.5 months, ORR4 strongly favored BV (56%) compared to physician’s choice (13%). Median PFS was also superior with BV (16.7 months) than physician’s choice (3.5 months).
A quality-of-life index showed significantly greater symptom reduction with BV compared with physician’s choice.
Patients received a median of 12 cycles of BV vs 5.5 cycles of bexarotene and 3 cycles of methotrexate.
Grade 3–4 adverse events, all-cause/drug-related, were seen in 41%/29% with BV vs 47%/29% with physician’s choice. Serious adverse events were seen in 29% of patients in each arm. As expected, peripheral neuropathy was seen more with BV (67%) than with physician’s choice (6%). At last follow-up, most patients in the BV arm had improvement or resolution of peripheral neuropathy, Kim said.
Discontinuation due to adverse events occurred in 24% in the BV arm and 8% in the physician’s choice arm.
“The data from this randomized trial provide compelling evidence favoring BV over bexarotene or methotrexate in CD30-expressing CTCL,” said Kim.