ECHELON-1: trial | Bending the Curve: Trial by Trial

ECHELON-1

A Randomized, Open-label, Phase 3 Trial of A+AVD Versus ABVD as Frontline Therapy in Patients With Advanced Classical Hodgkin Lymphoma

Phase 3N = 1,334NCT01712490

Population

Previously untreated stage III or IV classic Hodgkin lymphoma; 664 assigned to A+AVD and 670 to ABVD.

Design

Open-label, multicentre, randomised phase 3 trial of brentuximab vedotin plus doxorubicin, vinblastine and dacarbazine (A+AVD) versus doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD), up to six cycles, in previously untreated stage III or IV classic Hodgkin lymphoma. Primary endpoint: modified progression-free survival as adjudicated by an independent review committee; key secondary endpoint: overall survival.

Primary endpoint

mPFS

Arms

A+AVD (experimental, n = 664): Brentuximab vedotin plus doxorubicin, vinblastine and dacarbazine, up to six cycles
ABVD (control, n = 670): Doxorubicin, bleomycin, vinblastine and dacarbazine, up to six cycles

People

Connors JM

mPFSHR 0.77 (95% CI 0.60–0.98)Δ 24-month mPFS+4.9 pointsOSHR 0.73 (95% CI 0.45–1.18)OSHR 0.59 (95% CI 0.40–0.88)Δ 72-month OS+4.5 pointsPFSHR 0.68 (95% CI 0.53–0.86)

Show the numbers

Results reported for ECHELON-1
Endpoint	Analysis	A+AVD	ABVD	Effect
mPFSITT (1334 randomised)Time to progression, death, or non-complete response with use of subsequent anticancer therapy, adjudicated by an independent review committee.	primarymedian follow-up 24.6 monthsConnors 2018	82.1% at 2 y (78.8–85.0%)	77.2% at 2 y (73.7–80.4%)	HR 0.77 (95% CI 0.60–0.98)P=0.04Difference of 4.9 percentage points at 2 years. Hazard ratio is for an event of progression, death, or modified progression.
OSITT (1334 randomised)	interimmedian follow-up 24.6 monthsConnors 2018	—	—	HR 0.73 (95% CI 0.45–1.18)P=0.20Interim overall survival analysis in the primary paper: 28 deaths with A+AVD and 39 with ABVD. The abstract marks the hazard ratio and P value as corrected.
OS	long term-updatemedian follow-up 73 monthsAnsell 2022	93.9% at 6 y (91.6–95.5%)	89.4% at 6 y (86.6–91.7%)	HR 0.59 (95% CI 0.40–0.88)P=0.00939 deaths in the A+AVD group and 64 in the ABVD group. Key secondary endpoint; separate report from the primary paper.
PFS	long term-updatemedian follow-up 73 monthsAnsell 2022	—	—	HR 0.68 (95% CI 0.53–0.86)Conventional progression-free survival (disease progression or death), reported with the overall survival analysis; the abstract gives the hazard ratio only.

Results reported for ECHELON-1
Endpoint	Analysis	A+AVD	ABVD	Effect
mPFSITT (1334 randomised)Time to progression, death, or non-complete response with use of subsequent anticancer therapy, adjudicated by an independent review committee.	primarymedian follow-up 24.6 monthsConnors 2018	82.1% at 2 y (78.8–85.0%)	77.2% at 2 y (73.7–80.4%)	HR 0.77 (95% CI 0.60–0.98)P=0.04Difference of 4.9 percentage points at 2 years. Hazard ratio is for an event of progression, death, or modified progression.
OSITT (1334 randomised)	interimmedian follow-up 24.6 monthsConnors 2018	—	—	HR 0.73 (95% CI 0.45–1.18)P=0.20Interim overall survival analysis in the primary paper: 28 deaths with A+AVD and 39 with ABVD. The abstract marks the hazard ratio and P value as corrected.
OS	long term-updatemedian follow-up 73 monthsAnsell 2022	93.9% at 6 y (91.6–95.5%)	89.4% at 6 y (86.6–91.7%)	HR 0.59 (95% CI 0.40–0.88)P=0.00939 deaths in the A+AVD group and 64 in the ABVD group. Key secondary endpoint; separate report from the primary paper.
PFS	long term-updatemedian follow-up 73 monthsAnsell 2022	—	—	HR 0.68 (95% CI 0.53–0.86)Conventional progression-free survival (disease progression or death), reported with the overall survival analysis; the abstract gives the hazard ratio only.

Hazard ratio (95% CI) by endpoint. Values below 1 favour the experimental arm.

Data table

Endpoint	HR	95% CI
mPFS	0.77	0.6–0.98
OS	0.73	0.45–1.18
OS	0.59	0.4–0.88
PFS	0.68	0.53–0.86

Appears in

2017 ECHELON-1: brentuximab vedotin plus AVD vs ABVD

Sources

Connors JM, Jurczak W, Straus DJ, Ansell SM, Kim WS, Gallamini A, et al. Brentuximab Vedotin with Chemotherapy for Stage III or IV Hodgkin's Lymphoma. N Engl J Med. 2018;378(4):331-344.
PubMed DOI
Ansell SM, Radford J, Connors JM, Długosz-Danecka M, Kim WS, Gallamini A, et al. Overall Survival with Brentuximab Vedotin in Stage III or IV Hodgkin's Lymphoma. N Engl J Med. 2022;387(4):310-320.
PubMed DOI