Phase 3 study of brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine (A plus AVD) versus doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) as front-line treatment for advanced classical Hodgkin lymphoma (HL): Echelon-1 study

Stephen Maxted Ansell, Anas Younes, Joseph M. Connors, Andrea Gallamini, Won Seog Kim, Jonathan W. Friedberg, Tatyana A. Feldman, Graham Collins, Nancy Bartlett, Jingyuan Wang, Kelly Brady, Jessica Sachs, Dirk Huebner, Naomi N. H. Hunder, John Radford

Research output: Contribution to journalMeeting Abstractpeer-review

Abstract

Background: Brentuximab vedotin (ADCETRIS), a CD30-targeted antibody-drug conjugate, has been approved for adults with relapsed or refractory CD30+ HL in 39 countries including the US and Europe. Front-line ABVD achieves complete response (CR) rates of 70–80% in patients (pts) with advanced HL. However, 10–20% of pts are refractory to front-line treatment and an additional ≤25% relapse. Further, bleomycin-induced pulmonary toxicity occurs in 10–25% of pts (Horning, J Clin Oncol 1994). In pts with relapsed HL post-autologous stem cell transplantation, objective response rate to single-agent brentuximab vedotin is 75% (CR, 33%; Chen, ASH 2012). In a ph 1 dose-escalation study (NCT01060904), 51 pts with treatment-naïve HL stage IIA bulky or stage IIB–IV disease were enrolled to evaluate safety, maximum tolerated dose and antitumor activity of brentuximab vedotin combined with ABVD (A+ABVD) or AVD (A+AVD) (Younes, Lancet Oncol 2013). 80% pts had stage III–IV, 25% had International Prognostic Score ≥4. Brentuximab vedotin was given on days 1 and 15 of 28-day cycles (≤6 cycles), 25 pts received ABVD plus brentuximab vedotin at 0.6, 0.9, or 1.2 mg/kg; 26 received AVD plus brentuximab vedotin 1.2 mg/kg. A+AVD was associated with a PET2 negative rate of 92%, CR rate of 96% and manageable toxicity. Although A+ABVD induced an unacceptably high rate of pulmonary toxicity compared to known rates with ABVD alone, pulmonary toxicity was not observed in the A+AVD cohort. We hypothesized that substituting bleomycin with brentuximab vedotin may improve progression-free survival (PFS) compared to ABVD and, eliminate bleomycin-related pulmonary toxicity. Methods: ECHELON-1 (NCT01712490), an ongoing, open-label, randomized, ph 3 study, will compare A+AVD vs ABVD in 1,040 pts with untreated stage III/IV classical HL. Pts will receive A+AVD (brentuximab vedotin 1.2 mg/kg with each dose of AVD) or ABVD on Days 1 and 15 of 28-day cycles (≤6 cycles). Primary endpoint: modified PFS (death, progression, receipt of chemotherapy or radiotherapy by pts not in CR after completing front-line therapy).
Original languageEnglish
Article numberTPS8613
JournalJournal of Clinical Oncology
Volume32
Issue number15 supplement
DOIs
Publication statusPublished - 20 May 2014
Event50th Annual Meeting of the American Society of Clinical Oncology - McCormick Place, Chicago, United States
Duration: 30 May 20143 Jun 2014

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