Juan Pablo Muñoz Pérez1, Jordi Muchart2, Vicente Santa-María López1,3, Mariona Suñol Capella4, Noelia Salvador5, Sara Pérez Jaume5, Ofelia Cruz Martínez1,3, Andrés Morales La Madrid6,7. 1. Pediatric Hematology and Oncology, Hospital Sant Joan de Déu, Barcelona, Spain. 2. Pediatric Neuroradiology Unit, Hospital Sant Joan de Déu, Barcelona, Spain. 3. Pediatric Neuro-Oncology Unit, Department of Oncology, Hospital Sant Joan de Déu, Passeig Sant Joan de Deu 2, 08950, Barcelona, Spain. 4. Department of Pathology, Hospital Sant Joan de Déu, Barcelona, Spain. 5. Developmental Tumor Biology Laboratory, Hospital Sant Joan de Déu, Barcelona, Spain. 6. Pediatric Hematology and Oncology, Hospital Sant Joan de Déu, Barcelona, Spain. amorales@sjdhospitalbarcelona.org. 7. Pediatric Neuro-Oncology Unit, Department of Oncology, Hospital Sant Joan de Déu, Passeig Sant Joan de Deu 2, 08950, Barcelona, Spain. amorales@sjdhospitalbarcelona.org.
Abstract
PURPOSE: Pediatric low-grade gliomas are the most frequent brain tumors in children. The standard approach for symptomatic unresectable tumors is chemotherapy. Recently, key molecular alterations/pathways have been identified and targeted drugs developed and tested in clinical trials. We describe our institutional experience with MAPK pathway targeted therapy. METHODS: We retrospectively reviewed the medical reports of 23 patients diagnosed with PLGG and treated with either trametinib or dabrafenib at Hospital Sant Joan de Dèu (Barcelona, Spain). Patients with neurofibromatosis were excluded. Objective response rate (ORR) and disease control rate (DCR) were determined using the Response Assessment in Pediatric Neuro-Oncology criteria in low-grade glioma. ORR was defined as the proportion of patients with the best overall response including complete remission (CR) or partial remission (PR). DCR was the sum of the CR, PR, and stable disease (SD) rates. RESULTS: ORR with trametinib was 0% (95% CI, 0%-23.2%) and DCR was 78.6% (95% CI, 49.2%-95.3%). Eleven patients had SD and three patients presented PD. ORR with dabrafenib was 41.7% (95% CI, 16.5%-71.4%), including four CR and one patient with PR. DCR with dabrafenib was 100% (95% CI, 73.5%-100%); there were seven SD and none PD. Treatment was well tolerated. Only three patients, on trametinib, presented grade 3 adverse effects: leukocytoclastic vasculitis, cheilitis, and bone infection. CONCLUSIONS: Our experience adds to the growing data about the efficacy and tolerability of targeted therapy in patients with PLGG. When present, toxicity is mainly mild-moderate and transient. Ongoing prospective clinical trials are trying to address if its use should be advanced to first-line therapy.
PURPOSE: Pediatric low-grade gliomas are the most frequent brain tumors in children. The standard approach for symptomatic unresectable tumors is chemotherapy. Recently, key molecular alterations/pathways have been identified and targeted drugs developed and tested in clinical trials. We describe our institutional experience with MAPK pathway targeted therapy. METHODS: We retrospectively reviewed the medical reports of 23 patients diagnosed with PLGG and treated with either trametinib or dabrafenib at Hospital Sant Joan de Dèu (Barcelona, Spain). Patients with neurofibromatosis were excluded. Objective response rate (ORR) and disease control rate (DCR) were determined using the Response Assessment in Pediatric Neuro-Oncology criteria in low-grade glioma. ORR was defined as the proportion of patients with the best overall response including complete remission (CR) or partial remission (PR). DCR was the sum of the CR, PR, and stable disease (SD) rates. RESULTS: ORR with trametinib was 0% (95% CI, 0%-23.2%) and DCR was 78.6% (95% CI, 49.2%-95.3%). Eleven patients had SD and three patients presented PD. ORR with dabrafenib was 41.7% (95% CI, 16.5%-71.4%), including four CR and one patient with PR. DCR with dabrafenib was 100% (95% CI, 73.5%-100%); there were seven SD and none PD. Treatment was well tolerated. Only three patients, on trametinib, presented grade 3 adverse effects: leukocytoclastic vasculitis, cheilitis, and bone infection. CONCLUSIONS: Our experience adds to the growing data about the efficacy and tolerability of targeted therapy in patients with PLGG. When present, toxicity is mainly mild-moderate and transient. Ongoing prospective clinical trials are trying to address if its use should be advanced to first-line therapy.
Authors: Axel Hauschild; Jean-Jacques Grob; Lev V Demidov; Thomas Jouary; Ralf Gutzmer; Michael Millward; Piotr Rutkowski; Christian U Blank; Wilson H Miller; Eckhart Kaempgen; Salvador Martín-Algarra; Boguslawa Karaszewska; Cornelia Mauch; Vanna Chiarion-Sileni; Anne-Marie Martin; Suzanne Swann; Patricia Haney; Beloo Mirakhur; Mary E Guckert; Vicki Goodman; Paul B Chapman Journal: Lancet Date: 2012-06-25 Impact factor: 79.321
Authors: Jason Fangusaro; Olaf Witt; Pablo Hernáiz Driever; Asim K Bag; Peter de Blank; Nadja Kadom; Lindsay Kilburn; Robert M Lober; Nathan J Robison; Michael J Fisher; Roger J Packer; Tina Young Poussaint; Ludmila Papusha; Shivaram Avula; Alba A Brandes; Eric Bouffet; Daniel Bowers; Anton Artemov; Murali Chintagumpala; David Zurakowski; Martin van den Bent; Brigitte Bison; Kristen W Yeom; Walter Taal; Katherine E Warren Journal: Lancet Oncol Date: 2020-06 Impact factor: 41.316
Authors: Emily Y Chu; Karolyn A Wanat; Christopher J Miller; Ravi K Amaravadi; Leslie A Fecher; Marcia S Brose; Suzanne McGettigan; Lydia R Giles; Lynn M Schuchter; John T Seykora; Misha Rosenbach Journal: J Am Acad Dermatol Date: 2012-05-18 Impact factor: 11.527