Brentuximab vedotin continues to demonstrate superior clinical activity in classical Hodgkin lymphoma

Additional analysis and 3-year update of results from ECHELON-1, a frontline phase 3 trial evaluating brentuximab vedotin in combination with doxorubicin, vinblastine, and dacarbazine (AVD) compared with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) in stage III or IV frontline classical Hodgkin lymphoma (HL) patients, resulted in a statistically significant improvement in modified progression-free survival (PFS) for the brentuximab vedotin + AVD arm versus the control arm of ABVD, as assessed by independent review [1].

Brentuximab vedotin is an antibody-drug conjugate directed to CD30, a defining marker of classical HL and expressed on the surface of several types of peripheral T-cell lymphomas. The intention-to-treat analysis examined PFS outcomes per investigator assessment in the population of 1,334 patients <60 years old at 3 years, by cycle 2 positron-emission tomography (PET2). The ECHELON-1 trial achieved its primary endpoint with the combination of brentuximab vedotin plus AVD resulting in a statistically significant improvement in modified PFS vs the control arm of ABVD, as assessed by independent review facility (HR 0.77; P=0.035). Modified PFS was defined as time to progression, death, or evidence of non-complete response after completion of frontline therapy per independent review facility followed by subsequent anticancer therapy. Key findings from this updated analysis include:

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    • The 3-year PFS for all patients in the brentuximab vedotin + AVD arm was 83.1% compared with 76% in the ABVD arm (HR 0.70), a difference of 7.1%.
    • PFS benefit at 3 years for brentuximab vedotin + AVD was observed for all patients independent of PET2 status, including in patients <60 years old.
      
      
      
      • PET2-scan was negative in 85.8% in the brentuximab vedotin + AVD arm compared with 79.5% in the ABVD arm (HR 0.69), a difference of 6.3%.
      • PET2-scan result was positive in 67.7% in the brentuximab vedotin + AVD arm compared with 51.5% in the ABVD arm (HR 0.59), a difference of 16.2%.
    • Consistently higher PFS was observed among patients treated with brentuximab vedotin + AVD compared with ABVD across most pre-specified subgroups, including disease stage, age, and prognostic score.
    • In the brentuximab vedotin + AVD arm, peripheral neuropathy events were observed in 67% of patients compared with 43% in the ABVD arm. The 3-year analysis shows that among patients with peripheral neuropathy, 78% of in the brentuximab vedotin + AVD arm and 83% in the ABVD arm reported complete resolution or improvement at last follow-up.

 

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   1. Horwitz S, et al. Abstract S820, 24th Congress of the EHA, 13-16 June 2019, Amsterdam, the Netherlands.

 



Posted on 9 August, 201911 March, 2021