BEACOPP or ABVD?

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%
CR, CRU, PR > 80%
RT on bulk
or residual mass
(30 Gy)
RT on bulk
or residual mass
(30 Gy)
R< 80%, PD, Relapse
High-dose
Salvage + RT
(20-25 Gy)
Viviani S et al, 2011
R< 80%, PD, Relapse
High-dose
Salvage + RT
(20-25 Gy)
Viviani S et al, 2011
Freedom from first progression
P
R
O
B
A
B
I
L
I
T
Y
1.00
86%
.50
.25
BEACOPP
Pts
155
Events
18
ABVD
166
42
1
2
3
P
R
O
B
A
B
I
L
I
T
Y
85%
69%
70%
.75
Event-free survival
HR
0.43
4
p
0.01
5
1.00
80%
1.00
91%
85%
.25
.75
.50
.25
BEACOPP
Pts
155
ABVD
166
1
2
Events
11
HR
0.61
p
0.17
20
3
4
5
Years
Pts
155
166
BEACOPP
ABVD
1
2
Events
29
43
HR
0.69
3
p
0.12
5
4
Years
Overall Survival
P
R
O
B
A
B
I
L
I
T
Y
82%
69%
.50
Years
88%
72%
.75
Freedom from second progression
P
R
O
B
A
B
I
L
I
T
Y
78%
1.00
90%
87%
89%
86%
.75
.50
.25
BEACOPP
Pts
155
ABVD
166
1
2
Events
14
HR
1.03
p
0.94
15
3
4
5
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
ABVD
MOPP
SINGLE AGENT
BEACOPP
ABVD
MOPP
SINGLE AGENT
BEACOPP
ABVD
ABVD
MOPP
MOPP
SINGLE AGENT
SINGLE AGENT
BEACOPP
Evidence for OS with BEACOPP escalated
Probability
1.00
0.90
0.80
Regimen
5-year OS difference
6*BEACOPP esc
vs. ABVD
10%
(95% CI : 13% to 5%)
0.70
0.60
ABVD
6*BEACOPP esc
0.50
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
(…)
Still BEACOPP or no BEACOPP?
BEACOPP defenders
ABVD defenders
BEACOPP or
Europe
BEACOPP defenders
ABVD?
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%)
TOTAL412 (3)
401 (2)
374
(2) 346 (3 ) 297
(1) 227 (2)
OS at 3Y:
13/335 (95.8%)
159 (3)
88
(1)
28 (0)
1
(0)
By courtesy of A. Gallamini, January 30, 2014
HD0607: OS by PET2 diagnosis
* 1 pt died before
performing PET2
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%)
P=0.0020
MEDIAN FUP PET2 pos 844 days
(q1 483 – q3 1088)
MEDIAN FUP PET2 neg 972 days
(q1 722 – q3 1241)
PET2 NEG
PET2 POS
335 (0)
76 (2)
331 (2)
70 (0)
311 (0)
63 (2)
290 (1)
56 (2)
252 (0)
45 (1)
196 (2)
31 (0)
140 (3)
19 (0)
73
15
(1)
(0)
24 (0)
4 (0)
1
0
(0)
(0)
By courtesy of A. Gallamini, January 30, 2014
…….. As the H2 Study
Study
Network
Study
start
Initial
Therapy
H2
Israel
2006
2 ABVD
H2
Israel
2006
Subsequent
Therapy
ABVD or BEACOPP 0-2
according to PET
2 BEACOPPesc BEACOPP or ABVD 3-7
according to PET
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
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.

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