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The ECHELON-2 trial: Results of a randomised, double-blind, active-controlled phase 3 study of brentuximab vedotin and CHP (A plus CHP) vs CHOP in the frontline treatment of patients (pts) with CD30(+) peripheral T-cell lymphomas (PTCLs)

Trumper, L.
; 
O'Connor, O. A.
; 
Pro, B.
; 
Illidge, Timothy M
; 
Advani, R. H.
; 
Bartlett, N. L.
; 
Christensen, J. H.
; 
Morschhauser, F.
; 
Domingo-Domenech, E.
; 
Rossi, G.
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Abstract
Introduction: Upfront treatment of PTCL, an aggressive form of NHL, with CHOP/CHOP-like regimens does not achieve durable remissions in most PTCL pts. Based on encouraging phase 1 results (Fanale M, et al. Blood 2018), the ECHELON-2 study was initiated to compare efficacy and safety of A+CHP vs CHOP for CD30+ PTCL treatment. Methods: ECHELON-2 is a randomised, double-blind, active-controlled, international trial in previously-untreated CD30+ (?10% of neoplastic cells/infiltrate by local review) adult PTCL pts (targeting 75% systemic anaplastic large cell lymphoma [sALCL] pts); ALK+ sALCL pts were required to have an IPI ?2. The primary endpoint, PFS per blinded independent review, was analysed by intent-to-treat (ITT). Key secondary endpoints were OS, PFS in sALCL, CR rate, and objective response rate (ORR). Pts were stratified by histological subtype and IPI score, and randomised 1:1 to 21day cycles of CHOP or A+CHP for 6-8 cycles. Consolidative SCT/radiotherapy was allowed at investigatorĀ“s discretion after end of treatment. Results: Between Jan 2013 and Nov 2016 452 pts were enrolled. Median age was 58 years (range, 18-85), pts had an ECOG PS of 0 (39%), 1 (39%), or 2 (22%); most had Stage III (27%) or IV disease (53%) at diagnosis; 78% had IPI scores ?2 (2 [34%], 3 [29%], 4 [12%], 5 [3%]). 70% of pts had sALCL (ALK+, 22%; ALK-, 48%). As of April 2018, 449/452 pts had received ?1 dose of study therapy; all pts had either completed therapy (82%) or discontinued due to adverse events (AEs) (7%), progressive disease (7%), investigator decision (2%), or pt decision (2%). A+CHP provided significant, clinically-meaningful improvement in efficacy in the ITT population, including OS benefits. All primary and alpha-controlled key secondary endpoints were met. Hazard ratios of PFS (0.71 [95% CI: 0.54-0.93], P=0.01) and OS (0.66 [95% CI: 0.46-0.95], P=0.02) favoured A+CHP over CHOP. ORR was 79% (95% CI: 75.4-83.1); complete response rate was 64% (95% CI: 59.1-68.2). With a median 35.2 month follow-up, 3-year PFS was 52.9% (95% CI: 47.7-57.7) and OS was 73.1% (95% CI: 68.3-77.2) for all pts. AE profiles were consistent with known brentuximab vedotin and CHOP safety profiles, including peripheral sensory neuropathy (43%). Grade ?3 AEs in ?10% of pts were neutropenia (33%), febrile neutropenia (17%), and anaemia (12%). Conclusions: Frontline A+CHP was superior to CHOP for CD30+ PTCL pts, as shown by significant increases in PFS and OS, with a manageable safety profile,
Authors
Trumper, L.
O'Connor, O. A.
Pro, B.
Illidge, Timothy M
Advani, R. H.
Bartlett, N. L.
Christensen, J. H.
Morschhauser, F.
Domingo-Domenech, E.
Rossi, G.
Kim, W. S.
Feldman, T. A.
Lennard, A.
Belada, D.
Illes, A.
Tobinai, K.
Tsukasaki, K.
Yeh, S. P.
Shustov, A. R.
Huttmann, A.
Savage, K. J.
Yuen, S.
Iyer, S.
Zinzani, P. L.
Hua, Z.
Little, M.
Rao, S.
Woolery, J.
Manley, T.
Horwitz, S. M.
Affiliation
Univ Med Gottingen, Dept Hematol & Oncol, Gottingen, Germany
Description
Date
2019
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All Christie Publications
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Meetings and Proceedings
Citation
Trumper L, O'Connor OA, Pro B, Illidge TM, Advani RH, Bartlett NL, et al. The ECHELON-2 trial: Results of a randomised, double-blind, active-controlled phase 3 study of brentuximab vedotin and CHP (A plus CHP) vs CHOP in the frontline treatment of patients (pts) with CD30(+) peripheral T-cell lymphomas (PTCLs) Oncology Research and Treatment. 2019;42:23-
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URI
http://hdl.handle.net/10541/623443
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