ABVD or BEACOPP for advanced Hodgkin lymphoma Not to BEACOPP Massimo Federico University of Modena and Reggio Emilia Italy
What is the best Induction Therapy for Advanced Hodgkin Lymphoma?
How to treat patients with advanced Hodgkin Lymphoma (HL)? There is a general agreement that BEACOPPesc is associated with better disease control in terms of response rate, progression free survival and freedom from treatment failure. However, there is no agreement on the superiority of BEACOPPesc over ABVD in terms of Overall Survival (OS).
Standard and increased-dose BEACOPP vs COPP-ABVD for advanced HL Freedom from Treatment Failure Overall Survival HD9 trial BEACOPP is superior to COPP/ABVD Diehl V et al, 348(24):2386-2395, 2003
. and outside GHSG???
GISL HD2000: ABVD vs CEC vs BEA Federico M et al. 2009
Advanced stage: ABVD vs BEACOPP HL disease Stage IIB-IV Stratify: Site; IPS 2 vs 3 Random 1:1 ABVD x 6-8 BEACOPP exc x 4 BEACOPP std x 4 CR, CRU, PR > 80% RT on bulk or residual mass (30 Gy) R< 80%, PD, Relapse High-dose Salvage + RT (20-25 Gy) CR, CRU, PR > 80% RT on bulk or residual mass (30 Gy) R< 80%, PD, Relapse High-dose Salvage + RT (20-25 Gy) Viviani S et al, 2011
Viviani S et al, 2011 Freedom from first progression P R O B A B I L I T Y 1.00.75.50.25 BEACOPP ABVD Pts Events HR p 155 18 0.43 0.01 166 42 86% 85% 70% 69% P R O B A B I L I T Y 1.00.75.50.25 Event-free survival 80% 78% 72% 69% BEACOPP Pts 155 Events 29 HR 0.69 p 0.12 ABVD 166 43 1 3 4 5 2 Years 1 3 4 5 2 Years Freedom from second progression P R O B A B I L I T Y 1.00.75.50.25 BEACOPP ABVD Pts Events HR p 155 11 0.61 0.17 166 20 91% 88% 85% 82% P R O B A B I L I T Y 1.00.75.50.25 Overall Survival BEACOPP ABVD 90% 89% Pts Events HR p 155 14 1.03 0.94 166 15 87% 86% 1 3 4 5 2 Years 1 3 4 5 2 Years
EORTC releases final results of advanced Hodgkin Lymphoma study comparing BEACOPP to ABVD (EORTC 20012) At a median follow up of 3.9 years, event free survival, the primary endpoint, was similar between treatment arms. More progressions/ relapses were observed with ABVD than with BEACOPP treatment, while early discontinuations were more frequent with BEACOPP. In this high-risk group, overall survival was not significantly improved with BEACOPP. 2012: P. Carde, as of June 2012
Viviani, NEJM 2011 Carde, ASCO 2012 BEACOPP BEACOPP ABVD ABVD BEACOPP ABVD MOPP MOPP ABVD MOPP SINGLE AGENT SINGLE AGENT MOPP SINGLE AGENT BEACOPP SINGLE AGENT
Probability Evidence for OS with BEACOPP escalated 1.00 0.90 0.80 0.70 0.60 Regimen 6*BEACOPP esc vs. ABVD 5-year OS difference 10% (95% CI : 13% to 5%) 0.50 ABVD 6*BEACOPP esc 0 1 2 3 4 5 6 Years
it is premature to conclude that the magnitude of OS benefit as estimated by the network analysis is real
HD9 trial: 10 years of follow up Arm A= COPP/ABVD, Arm B= BEACOPP baseline, Arm C= BEACOPP escalated Freedom from Treatment Failure Overall Survival Engert A et al, 27(27):4548-54, 2009
Borchmann P et al, 2011 A Residual disease after CHT (w/wo initial bulky) B Initial bulky, no residual disease
FFTF TTP Engert A et al, 2012 OS
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Still BEACOPP or no BEACOPP? BEACOPP defenders ABVD defenders
BEACOPP or ABVD? Europe BEACOPP defenders USA/UK/Canada ABVD defenders Modified from Massimo Federico
Could the treatment of patients with advanced HL according to Risk and Response be the solution?
Outcome according to IPS: GISL HD2000 BEA vs ABVD CEC vs ABVD P=.125 P=.676 BEA vs ABVD CEC vs ABVD P=.038 P=.056 Federico M et al, 2009
Relative risk of chemoresistance Clin Lymphoma Myeloma Leuk Gobbi PG et al, 2011
May 2008 July 2008 Sept 2008
HD0607: Overall Survival n = 412 OS at 2Y: 10/412 (97.3%) OS at 3Y: 13/335 (95.8%) TOTAL412 (3) 401 (2) 374 (2) 346 (3 ) 297 (1) 227 (2) 159 (3) 88 (1) 28 (0) 1 (0) By courtesy of A. Gallamini, January 30, 2014
* 1 pt died before performing PET2 HD0607: OS by PET2 diagnosis n = 411* OS at 2Y: PET2 NEG: 3/335 (99.0%) PET2 POS: 6/76 (90.4%) OS at 3Y: PET2 NEG: 5/335 (97.8%) PET2 POS: 7/76 (88.2%) MEDIAN FUP PET2 pos 844 days ( q1 483 q3 1088) MEDIAN FUP PET2 neg 972 days ( q1 722 q3 1241) P=0.0020 PET2 NEG 335 (0) 331 (2) 311 (0) 290 (1) 252 (0) 196 (2) 140 (3) 73 (1) 24 (0) 1 (0) PET2 POS 76 (2) 70 (0) 63 (2) 56 (2) 45 (1) 31 (0) 19 (0) 15 (0) 4 (0) 0 (0) By courtesy of A. Gallamini, January 30, 2014
.. As the H2 Study Study Network Study start Initial Therapy Subsequent Therapy H2 Israel 2006 2 ABVD ABVD or BEACOPP according to PET H2 Israel 2006 2 BEACOPPesc BEACOPP or ABVD according to PET IPS 0-2 3-7 T110 TAILORED THERAPY IN HODGKIN LYMPHOMA, BASED ON PREDEFINED RISK FACTORS AND EARLY INTERIM PET/CT, ISRAELI H2 PROTOCOL: PRELIMINARY REPORT ON 317 PATIENTS Dann EJ
IPS 0-2 Start with ABVD or ECHELON1
IPS 3-7 Start with BEACOPPesc or
Thus, taking advantage of all.. RISK B-V RESPONSE
Conclusion Data emerging from several randomized controlled trials of a response-oriented approach driven by early PET assessment, and the potential of brentuximab vedotin combinations to improve the efficacy of ABVD with an acceptable toxicity profile, allow us to conclude that the recommendation to give all patients six cycles of BEACOPPesc upfront is not appropriate.