Aktuelle Studien- und Therapiekonzepte der GHSG Peter Borchmann University Hospital Cologne 19.03.2014 1
Das Hodgkin Lymphom Wie wenig Therapie braucht das frühe Stadium? Ist die Strahlentherapie PET-gesteuert verzichtbar?
Kann Bleomycin im ABVD Schema weggelassen werden? HD13 ABVD vs. AVD 1.0 0.9 0.8 FFTF 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0.0 5 year estimate [95%-CI] 2xABVD+IF: 93.1% [90.7% to 95.5%] 2xAVD+IF: 89.2% [86.3% to 92.2%] difference: 3.9% [0.1% to 7.7%] Hazard Ratio [95%-CI]* 1.50 [1.00 to 2.26] ABVD AVD non inferiority margin of 1.72 not excluded non inferiority cannot be concluded 0 12 24 36 48 60 72 Pts. at Risk Time [months] ABVD 566 533 500 437 326 207 120 AVD 571 541 496 439 320 213 117 Behringer et al., Haematologica, 2013, 11
Kumulative Brustkrebs-Inzidenz und Alter bei ED des HL (1,122 female 5-year survivors treated for HL <51 years between 1965 and 1995) De Bruin et al. JCO 2009; 27(26): 4239-4246
PET- nach Chemo: keine Radiatio mehr nötig? RAPID Involved field radiotherapy versus no further treatment in patients with clinical stages IA/IIA Hodgkin lymphoma and a negative PET scan after 3 cycles ABVD. Results of the UK NCRI RAPID trial PFS inferior 6,3% exceeding margin of 7% H10 RANDOMIZED TRIAL ON EARLY FDG- PET SCAN GUIDED TREATMENT ADAPTATION IN STAGES I/II HODGKIN LYMPHOMA PFS inferior including lower margin of 10% 19.03.2014 5
Early favorable : Die aktuelle GHSG HD16-Studie CS I/II without RF Experimental arm 2 x ABVD PET (+/-) 2 x ABVD PET- 2 x ABVD PET+ 20 Gy IF Follow up 20 Gy IF
Early unfavorable Stadien: GHSG HD17-Studie Experimental arm 2x BEACOPPesc 2 x ABVD PET (+/-) 2x BEACOPPesc 2 x ABVD PET 30 Gy IF PET - PET + Follow up Follow up 30 Gy IN
Das Hodgkin Lymphom
Was sollte der standard of care sein? ABVD ist genauso wirksam wie BEACOPP, aber weniger toxisch Brauchen wir denn wirklich BEACOPP? 19.03.2014 9
What are the results of these standards today? Standard defining study results: Study IIL Viviani et al NEJM 2011 HD15 Engert et al Lancet 2012 Group Median FU 6 8 x ABVD 61 168 73 6x BEACOPPes c n PFS (%) Diff. (%) 60 610 90 17 OS (%) Diff. (%) 84 11 95 19.03.2014 10
DIRECT comparisons of ABVD vs BEACOPP-variants: efficacy Study Group n 5 y PFS Difference (%) p 5 y OS HD 2000 ABVD 99 68 84 BEACOPP 13 0.038 98 81 92 (4 esc + 2 std) IIL ABVD 168 73 84 BEACOPP 12 0.004 163 85 89 (4 esc + 4 std) ABVD 275 69 86,7 IG 20012 15 0.0003 BEACOPP 274 84 90,3 (4 esc + 4 std) ABVD 77 75 92 LYSA H34 IPS 0 2 BEACOPP 18 0.008 68 93 99 (4 esc + 4 std) HD15 7 year PFS; 4 year PFS. 6 BEACOPPesc 711 91 95.3 Difference (%) 8 5 4 7
Generating evidence in metaanalyses for OS C 1.00 ABVD versus 6 * BEACOPP esc 0.90 Probability 0.80 0.70 0.60 Regimen 6*BEACOPPesc 5 year OS difference 10% (95% CI: 13% to 5%) 0.50 ABVD 6*BEACOPPesc 0 1 2 3 4 5 6 Years 19.03.2014 12
Hit it hard and early
How can we improve BEACOPP escalated? Considerations for Individual Treatment Efficacy Morbidity Modified figure from Sandra Horning, Stanford, CA
Modified and targeted BEACOPP Medikament BrECADD comment: Bleomycin pulmonary-toxicity Etoposide 150 Adriamycin 40 Cyclophosphamide 1250 Vincristine neurotoxicity Brentuximab vedotin 1.8 Procarbazine Prednisone gonadal toxicity Cushing, infections Dacarbazine 2x 250 Dexamethasone 4x 40
Targeted BEACOPP: Study flow Randomisation Patients aged 18 60 CS IIB + RF ED or LMM, CS III/IV 2 x BrECAPP 2 x BrECADD Off study in case of PD Interim Staging (CT-2/PET-2) Off study in case of PD 4 x BrECAPP 4 x BrECADD End of therapy AND residual nodes > 2.5 cm: PET positiv: Rx @30 Gy PET negative: Follow up 19.03.2014 16
Klinikum Bayreuth 1 Berlin, Campus Virchow 6 Bielefeld Dr. Schäfer/ Dr. Just/ Dr. Görner/ Dr. Düwel 3 Klinikum Bremen Mitte ggmbh 3 Städtisches Klinikum Braunschweig 1 Universitätsklinik Essen Hämatologische Tagesklinik 4 Klinikum Fulda, Tumorklinik, MVZ Osthessen 1 Hamburg Asklepios Klinik St. Georg 1 Universitätsklinikum Heidelberg 9 Universitätsklinikum Jena 1 Städtisches Klinikum Karlsruhe 4 Universitätsklinik Schleswig Holstein Kiel 4 Universitätsklinik Köln 20 Nach 1 Jahr fertig. Mit Ihrer Hilfe. DANKE! Universitätsklinik Leipzig 4 Klinikum Großhadern München 11 Brüderkrankenhaus St. Josef Paderborn 2 Klinikum Ernst von Bergmann Potsdam 7 Eberhard Karls Universität Tübingen 5 Universitätsklinikum Ulm 2 Universitätsklinikum Würzburg 4 Gesamt 93 17
Treatment outcome after chemotherapy (primary endpoint) Treatment Outcome BrECAPP N = 22 BrECADD N = 24 Total N = 46 HD18 CR or PET negative PR 19 (86%) 22 (96%) 41 (91%) 95% CI: 83% 99% 91,9% Less than PR or PET positive 3 (14%) 1 (4%) 4 (9%) 95% CI: 2% 21% 7 % 19.03.2014 18
Acute Toxicities BRECADD (n=34) Type of Toxicity NCIC-CTC Grade none I II III IV III/IV HD18* III/IV (n=447) Hematological 1 (3%) 1 (3%) 3 (9%) 29 (85%) 32 (94%) 404 (90.4%) Organs (old CRF) 16 (47%) 12 (35%) 6 (18%) - - - 64 (14.3%) * randomized patients after introduction of amendment 2 receiving 4.6 cycles of BEACOPP esc
HL Management Results of the targeted-beacopp study will indicate, if we can maintain efficacy of BEACOPP escalated and improve its tolerability Considerations for Individual Treatment Efficacy Morbidity Modified figure from Sandra Horning, Stanford, CA
HD18: PET early response adpated design 2 x BEACOPP escalated centrally reviewed PET PET + Stellenwert von R wird aktuell ausgewertet 1x BEACOPPesc 5x BEACOPPesc 6x BEACOPPesc PET - 2x BEACOPPesc End of therapy AND residual nodes > 2.5 cm : PET positiv: Rx
Was machen wir mit den Älteren? Targeted CHOP : B-CAP d1 Brentuximab vedotin 1.8 mg/kg Cyclophosphamide 750 mg/m ² Doxorubicin 50 mg/m 2 d1-5 Predniso(lo)ne 100 mg day 1 day 8 day 15 recycle day 22 In Kooperation mit der NLG, Start Q2/14 3/19/2014 22
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