FDA Expands Adcetris’ Label in Hodgkin Lymphoma

The FDA has approved Adcetris (brentuximab vedotin) as a consolidation therapy following autologous stem cell transplantation (ASCT) in patients with Hodgkin lymphoma at risk of relapse or progression, based on the phase 3 AETHERA trial.

In the study, treatment with the drug reduced the risk of disease progression by 43 percent compared with placebo. The median progression-free survival (PFS) with Adcetris was 42.9 versus 24.1 months. Results from the study were presented at the 2014 American Society of Hematology Annual Meeting and subsequently published in The Lancet.

“The FDA approval of [Adcetris] for post-autologous hematopoietic transplantation consolidation treatment in classical Hodgkin lymphoma patients with high risk of relapse or progression is a significant milestone for patients and physicians,” lead investigator on the trial Craig Moskowitz, clinical director, Division of Hematologic Oncology, Memorial Sloan Kettering Cancer Center, said in a statement. “Approximately half of all Hodgkin lymphoma patients who undergo an autologous hematopoietic stem cell transplant will relapse, representing a significant need for additional treatment options to improve progression free survival.”

In the phase 3 study, 329 patients were randomized to receive Adcetris (165 patients) or placebo (164 patients). Adcetris was administered at 1.8 mg/kg intravenously every three weeks for a median of 15 cycles. A majority (60 percent) of patients treated in the study were refractory to frontline therapy. All patients were required to have obtained a complete remission (CR), partial remission (PR), or stable disease (SD) to salvage therapy prior to ASCT.

The median age of patients enrolled in the trial was 32 years. The median number of prior therapies was two (ranging from two to eight), with 47 percent of patients receiving greater than two prior therapies. Overall, 42 percent of patients had experienced a prior CR with salvage therapy, a PR for 34 percent, and SD in 24 percent. The primary endpoint of the study was PFS, with secondary endpoints focused on overall survival (OS) and safety.

The two-year PFS rate for patients treated with Adcetris following ASCT was 54 percent. For patients with primary-refractory disease, the two-year PFS rate was 60 percent with Adcetris compared with 42 percent for placebo.

The estimated two-year OS rates with Adcetris and placebo were both 88 percent. This endpoint was potentially confounded by crossover, as 85 percent of patients in the placebo arm received Adcetris when the trial was unblinded in September 2014.

The most common all-grade adverse events with Adcetris versus placebo were peripheral sensory neuropathy (56 vs 16 percent) and neutropenia (35 vs 12 percent). A majority (85 percent) of patients who experienced peripheral neuropathy with Adcetris had resolution of this adverse event within a median of 23.4 months. The primary cause of treatment discontinuation was progression.

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