Monika L. Metzger1, Jamie Flerlage1, Matthew Krasin2, Jörg M. Bartelt3, Amy Billett4, John K. Choi5, Matthew Ehrhardt1,6, Thomas Georgi7, Dirk Hasenclever8, Melissa Hudson1,6, Sue C. Kaste9, Regine Kluge7, Dieter Körholz10, Lars Kurch7, Michael Link11, Dietrich Stoevesandt3, Christine Mauz-Körholz10
1 Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN, 2 Department of Radiation Oncology, St. Jude Children's Research Hospital, Memphis, TN, 3 Clinic of Radiology, Medical Faculty of the Martin-Luther-University, Halle, Germany, 4 Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, MA, 5 Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN, 6 Department of Epidemiology and Cancer Control, St. Jude Children's Research Hospital, Memphis, TN, 7 Clinic for Nuclear Medicine, University of Leipzig, Leipzig, Germany, 8 Institute for Medical Informatics, Statistics & Epidemiology, University Leipzig, Germany, 9 Department of Diagnostic Imaging, St. Jude Children's Research Hospital, Memphis, TN, 10 Department of Pediatric Hematology and Oncology, Justus-Liebig University of Giessen, Germany and Medical Faculty of the Martin-Luther-University, Halle, Germany, 11 Division of Pediatric Hematology/Oncology, Stanford University School of Medicine
Background: Multiple recent studies have focused on omission of radiation in patients with an adequate early response. The GPOH, building up on their original experience with the OPPA/COPP regimen, demonstrated that 6 cycles OEPA/COPDAC with 20–30 Gy IFRT produced excellent results, with 5-year EFS and OS of approximately 87% and 95% respectively. In the EuroNet C1 trial about 30% of patients achieved an adequate response after 2 cycles of OEPA and could forgo radiation therapy.
Intervention: Substitution of vincristine with Brentuximab vedotin (Bv) in each cycle of OEPA/COPDac (AEPA/CAPDac) and 20 Gy ISRT to areas not in CR at early response evaluation (CR: > 50% volumetric anatomic response and Deauville < 4 on PET scan).
Eligibility: Stage IIB, IIIB and IV.
Objectives: To evaluate the safety and efficacy (defined as the number of patients with adequate response according to the definitions in the Euro-Net C1) of 2 cycles of AEPA.
Results: 71 patients were enrolled thus far in this ongoing multi-institutional trial between August 2013 and February 2018, with a median (range) age of 16 (6–19) years of age, 51% were female, 66% white and 75% had nodular sclerosing histology. Stage distribution was 18% stage IIB, 24% IIIB, 11% IVA and 45% IVB. There was one cardiac death (arrhythmia associated to pancarditis) during therapy. Therapy was in general well-tolerated. Most common adverse events being leukopenia and excessive weight gain. Peripheral neuropathy was reported only 4 times (all grade 1). Applying the EuroNet-C1 criteria for early response assessments to our first 32 patients, the proportion achieving an adequate response did not differ from that observed in Euronet C1, TG3 28% (90% CI [16; 44]).
Conclusions: AEPA/CAPDac is very well tolerated with a reassuring safety profile and minimal incidence of neuropathy. Substitution of vincristine by Bv in the first cohort of patients did not reduce the proportion of individuals requiring radiation compared to EuroNet C1 trial. While it is too early to make a statement regarding EFS, OS and other potential long-term benefits, the results thus far are promising. This is a PI initiated sponsored trial by Seattle Genetics Inc.