Abstract T086

EFFICACY and TOLERABILITY in DECOPDAC21 versus COPDAC28 in PEDIATRIC INTERMEDIATE and ADVANCED STAGE CLASSICAL HODGKIN LYMPHOMA: INTERIM RESULTS of the EURONET-PHL-C2 RANDOMIZED STUDY

Background: Cure rates in pediatric Hodgkin lymphoma (HL) exceed 95% with risk-adapted treatment. Involved field radiotherapy (IFRT) is still recommended in intermediate and advanced stage patients (pts) with inadequate response (IR), i.e. with a positive PET at early response assessment (ERA) after 2 OEPA (vincristine, etoposide, prednisone, doxorubicin) induction cycles. The EuroNetPHL-C2 trial aimed to reduce radiotherapy (RT) by testing intensified consolidation with DECOPDAC21 (doxorubicin, etoposide, cyclophosphamide, vincristine, prednisone, dacarbazine every 21 days) against standard COPDAC28 (cyclophosphamide, vincristine, prednisone, dacarbazine every 28 days). This is the first report of the interim analysis at 36 months observation.

Methods: This international open-label, randomized phase III study included pts with HL <25 years at diagnosis. All pts received OEPA followed by ERA. Further therapy was guided by treatment level (TL) according to risk factors of the EuroNet legacy trials, ERA and randomization arm. In intermediate (TL2) and advanced stages (TL3) either 2 or 4 COPDAC28 or DECOPDAC21 cycles were applied. PET-negative pts at ERA (adequate response, AR) received no RT. All ERA-IR pts received IFRT in the COPDAC28 arm. In DECOPDAC21 ERA-IR pts the decision on residual node RT was made at late response assessment (LRA). In case of LRA-AR, RT was completely omitted. PET thresholds for AR were Deauville scores 1-3 and qPET < 1.3, both at ERA and LRA. The primary objective was event-free survival (EFS), testing for non-inferiority in IR pts and superiority in AR pts.

Results: The intention to treat (ITT) TL2 and TL3 cohort comprised 2436 pts, 2261 were randomized. Of 2249 evaluable pts, 1445 had AR and 804 had IR after induction. In the ERA-AR group, 709 pts received DECOPDAC21 and had 96.0% EFS (95%CI 94.5%-97.5%) and 710 pts received COPDAC28 with 91.2% EFS (95%CI 89.1%-93.4%, p=0.0001). In the ERA-IR subgroup, 389 pts received DECOPDAC21 and had 85.7% EFS (95%CI 82.2%-89.3%) and 385 pts received COPDAC28 with 88.3% EFS (95%CI 85.1%-91.7%). In the DECOPDAC21 arms 12.8% received RT, whereas in COPDAC28, 35.6% received IFRT. In the ITT analysis 4/1445 AR pts (all COPDAC28) and 6/804 IR pts died, 2 in DECOPDAC21 and 4 in COPDAC28.

Conclusions: The novel DECOPDAC21 consolidation showed superior EFS in ERA-AR and non-inferiority in ERA-IR pts, allowing RT reduction in pediatric TL2 and TL3 pts without impacting treatment related mortality.

Authors

Dieter Körholz, Maurizio Mascarin, Judith Landman-Parker, Thierry Leblanc, Lars Kurch, Thomas W. Georgi, Regine Kluge, Dietrich Stoevesandt, Tanja Pelz, Dirk Vordermark, Karin Dieckmann, Stephen Daw, Ana Fernandez-Teijeiro, Galia Avrahami, Leanne Super, Auke Beishuizen, Walentyna Balwierz, Tomasz Klekawka, Anne Uyttebroeck, Andishe Attarbaschi, Michaela Cepelova, Francesco Ceppi, Alexander Fosså, Tim Prestidge, Annika Englund, Lisa Lyngsie Hjalgrim, Wolfram Klapper, Dirk Hasenclever, Christine Mauz-Körholz