6-year data from the ECHELON-1 study: How does combining brentuximab vedotin with chemotherapy affect overall survival of previously untreated cHL patients?
At this year's annual congress of the European Hematology Association (EHA), results from the analysis of 6-year data from the international randomized open-label phase III ECHELON-1 study on overall survival of patients with classical Hodgkin lymphoma (cHL) stage III/IV who received a combination of brentuximab vedotin with chemotherapy in the first-line treatment were presented, among other findings.
Introduction
For patients with classical Hodgkin lymphoma, improvements in overall survival (OS) compared to existing approaches have been rarely observed despite newly tested chemotherapeutic regimens in the first-line treatment. Reports of potential advancements in this area have been eagerly anticipated. In addition to findings from the pre-specified analysis of OS data after roughly 6 years of follow-up (completed on June 1, 2021), relevant safety data were also presented [1].
Improved long-term PFS with the A+AVD regimen
In the study, patients were randomized 1:1 to receive up to 6 cycles of brentuximab vedotin combined with doxorubicin, vinblastine, and dacarbazine (A+AVD regimen; n = 664) or doxorubicin with bleomycin, vinblastine, and dacarbazine (ABVD regimen; n = 670), administered on days 1 and 15 and then every 28 days [2].
From the 5-year data of ECHELON-1, it was already apparent that the A+AVD regimen could improve long-term progression-free survival (PFS) in patients who were previously untreated for cHL stage III/IV compared to ABVD. Regarding the long-term safety profile of the A+AVD combination, adverse events were manageable, and fewer secondary malignancies and more pregnancies were reported in the treatment arm compared to the ABVD arm (both arms were of equal size) [2].
“In the 5-year follow-up, the A+AVD combination showed a robust and sustained improvement in progression-free survival compared to ABVD, regardless of PET2 status, with a consistent safety profile. Based on these findings, the A+AVD combination should be preferred for patients with previously untreated classical Hodgkin lymphoma stage III or IV,” the authors conclude in their publication [2].
Overall survival after 6 years
Overall survival was a key secondary endpoint. Its evaluation was planned for the entire treated population (ITT − intention-to-treat), with a pre-specified interim analysis after 103 deaths [1].
Over a median follow-up period of 73 months, the A+AVD regimen showed significantly better results than ABVD – a statistically significant reduction in the risk of death by 41% (39 vs. 64 events in the OS endpoint; hazard ratio [HR] 0.590; 95% confidence interval [CI] 0.396–0.879; p = 0.009). Its use provided a consistent OS advantage across predefined subgroups, including patients with stage III (HR 0.863; 95% CI 0.452–1.648) or stage IV (HR 0.478; 95% CI 0.286–0.799) disease at diagnosis, patients who were PET-negative in cycle 2 (HR 0.583; 95% CI 0.338–0.856), and PET2-positive individuals (HR 0.163; 95% CI 0.037–0.717), individuals younger than 60 years (HR 0.509; 95% CI 0.291–0.890), as well as those aged ≥ 60 years (HR 0.829; 95% CI 0.469–1.466), and from different regions of the world (for Europeans HR 0.783; 95% CI 0.467–1.315; for North Americans HR 0.327; 95% CI 0.153–0.699) [1].
The A+AVD combination also showed better estimates for 6-year progression-free survival, at 82.3% vs. 74.5% (HR 0.678; 95% CI 0.532–0.863) [1].
Safety profile
The long-term safety profile was similar for the two treatment options mentioned. In both groups, peripheral neuropathy continued to resolve or improve with therapy, with 86% (379 out of 443) in the A+AVD arm and 87% (249 out of 286) in the ABVD arm showing complete resolution or improvement. Overall, 23 secondary malignancies were reported in the A+AVD arm and 32 in the ABVD arm [1].
Pregnancies, or live births, were reported by a greater number of patients undergoing A+AVD treatment (49 vs. 28, and 42 vs. 19, respectively, compared to patients receiving ABVD), and no live births were reported during the study period. No new safety signals were observed [1].
Conclusion
The authors believe that the statistically significant reduction in the risk of death, with consistent overall survival benefits across predefined subgroups, and the confirmation of the long-term manageability of the treatment in terms of its safety profile, support their proposal that the A+AVD combination should become the preferred therapeutic option for patients with previously untreated cHL stage III or IV [1].
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Sources:
1. Hutchings M., Ansell S. M., Straus D. J. et al. Improved overall survival with first-line brentuximab vedotin plus chemotherapy in patients with stage III/IV classical Hodgkin lymphoma: 6-year analysis of ECHELON-1. EHA 2022, abstract S200, 2022 Jun 10. Available at: www.library.ehaweb.org/eha/2022/eha2022-congress/357064/martin.hutchings.improved.overall.survival.with.first-line.brentuximab.vedotin.html
2. Straus D. J., Długosz-Danecka M., Connors J. M. et al. Brentuximab vedotin with chemotherapy for stage III or IV classical Hodgkin lymphoma (ECHELON-1): 5-year update of an international, open-label, randomised, phase 3 trial. Lancet Haematol 2021; 8 (6): e410–e421, doi: 10.1016/S2352-3026(21)00102-2.
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