NCOG-05. HEALTH-RELATED QUALITY OF LIFE (HRQOL) IN THE PHASE 2 FIREFLY-1 (PNOC026) TRIAL OF THE TYPE II RAF INHIBITOR TOVORAFENIB IN RELAPSED/REFRACTORY (R/R) PEDIATRIC LOW-GRADE GLIOMA (PLGG)

Abstract BACKGROUND Despite favorable long-term survival, ongoing disease and treatment-related morbidity substantially impact the HRQOL of patients with pLGG. Tovorafenib is a selective, CNS-penetrant, type II RAF inhibitor. Results from the ongoing FIREFLY-1 (NCT04775485) phase 2 study (Kilburn LK, et al. Nat Med. 2023) showed clinically meaningful responses and a manageable safety profile in pLGG. Vision remained stable or improved in 89% of evaluable patients with optic pathway gliomas (Nysom K, et al. Neuro-Oncol. 2023). METHODS FIREFLY-1 arm 1 patients 6 months–25 years of age with RAF-altered r/r pLGG received tovorafenib 420 mg/m2 weekly (600 mg max) in 28-day cycles. Exploratory measures included longitudinal assessment of PedsQL in patients ≥2 years of age. PedsQL 3.0 Cancer Module child self-reports Total Score and 8 subscales were used to assess HRQOL from 0 (worst)–100 (fewer problems/symptoms) (as of December 22, 2022) baseline (BL) to cycle 13 (C13) in patients ≥5 years of age. RESULTS For the PedsQL 3.0 Cancer Module, 51 completed self-reports at BL, and 32 at C13 due to continued attrition over time. Median Total Score was 81.5 (range: 46.3-100) at BL and 85.2 (range: 50-100) at C13. At C4, 16% worsened (decrease >10 points) and 11% improved (increase >10 points); by C13, 11% worsened and 33% improved. For Cognitive Problems, patients scored a median of 75 (range: 5-100) at BL and 85 (range: 20-100) at C13, with 11% and 26% improved at C4 and C13, respectively. A similar trend was seen with Nausea. Pain and Hurt remained even throughout (median: 87.5). Treatment Anxiety was not a major concern (median: 100, C1-C13); Procedural Anxiety improved over time (median: 58.3 BL; 79.2 at C13). CONCLUSIONS HRQOL generally remained stable, or improved, in the majority of patients with r/r pLGG during the first year of treatment with tovorafenib.

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Journal
Neuro-Oncology
Published
2024-11-01
DOI
https://doi.org/10.1093/neuonc/noae165.0887
Primary Topic
Neuroblastoma Research and Treatments
Type
article
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article

NCOG-05. HEALTH-RELATED QUALITY OF LIFE (HRQOL) IN THE PHASE 2 FIREFLY-1 (PNOC026) TRIAL OF THE TYPE II RAF INHIBITOR TOVORAFENIB IN RELAPSED/REFRACTORY (R/R) PEDIATRIC LOW-GRADE GLIOMA (PLGG)

Geoffrey McCowage, Daniel Landi, Nina Oestreicher, Darren Hargrave et al.
Neuro-Oncology
Neuroblastoma Research and Treatments
article

NCOG-05. HEALTH-RELATED QUALITY OF LIFE (HRQOL) IN THE PHASE 2 FIREFLY-1 (PNOC026) TRIAL OF THE TYPE II RAF INHIBITOR TOVORAFENIB IN RELAPSED/REFRACTORY (R/R) PEDIATRIC LOW-GRADE GLIOMA (PLGG)

Geoffrey McCowage, Daniel Landi, Nina Oestreicher, Darren Hargrave, Angela J. Waanders, Nicholas G. Gottardo, Jordan R. Hansford, Pablo Hernáiz Driever, Peter Manley, Devorah Segal, Nicolas U. Gerber, Jung Woo Han, John Devin Peipert, Sarah Leary, Lindsay Kilburn, David S. Ziegler, Nicholas Whipple, Valérie Larouche, Tim Hassall, Dong-Anh Khuong-Quang, Andrea Franson, Cassie Kline, Nada Jabado, Jasper van der Lugt, Susan Zelt, Michal Oren, Helen Toledano, Karsten Nysom, Hyoung Jin Kang, Mohamed Shebl Abdelbaki, Sébastien Perreault, Susan N. Chi, Patricia Baxter, Simon Bailey, Sabine Mueller, Liat Oren, Sandya Govinda Raju, Chris McKenna, Sandie Yu, Olaf Witt, Enrica E. K. Tan
article en

Abstract

Abstract BACKGROUND Despite favorable long-term survival, ongoing disease and treatment-related morbidity substantially impact the HRQOL of patients with pLGG. Tovorafenib is a selective, CNS-penetrant, type II RAF inhibitor. Results from the ongoing FIREFLY-1 (NCT04775485) phase 2 study (Kilburn LK, et al. Nat Med. 2023) showed clinically meaningful responses and a manageable safety profile in pLGG. Vision remained stable or improved in 89% of evaluable patients with optic pathway gliomas (Nysom K, et al. Neuro-Oncol. 2023). METHODS FIREFLY-1 arm 1 patients 6 months–25 years of age with RAF-altered r/r pLGG received tovorafenib 420 mg/m2 weekly (600 mg max) in 28-day cycles. Exploratory measures included longitudinal assessment of PedsQL in patients ≥2 years of age. PedsQL 3.0 Cancer Module child self-reports Total Score and 8 subscales were used to assess HRQOL from 0 (worst)–100 (fewer problems/symptoms) (as of December 22, 2022) baseline (BL) to cycle 13 (C13) in patients ≥5 years of age. RESULTS For the PedsQL 3.0 Cancer Module, 51 completed self-reports at BL, and 32 at C13 due to continued attrition over time. Median Total Score was 81.5 (range: 46.3-100) at BL and 85.2 (range: 50-100) at C13. At C4, 16% worsened (decrease >10 points) and 11% improved (increase >10 points); by C13, 11% worsened and 33% improved. For Cognitive Problems, patients scored a median of 75 (range: 5-100) at BL and 85 (range: 20-100) at C13, with 11% and 26% improved at C4 and C13, respectively. A similar trend was seen with Nausea. Pain and Hurt remained even throughout (median: 87.5). Treatment Anxiety was not a major concern (median: 100, C1-C13); Procedural Anxiety improved over time (median: 58.3 BL; 79.2 at C13). CONCLUSIONS HRQOL generally remained stable, or improved, in the majority of patients with r/r pLGG during the first year of treatment with tovorafenib.

Neuro-OncologyVol. 26(Supplement_8)
Northwestern University (US), Lurie Children's Hospital (US), Royal Children's Hospital (AU), St. Louis Children's Hospital (US), Primary Children's Hospital (US), Children's Hospital of Philadelphia (US), Children's National (US), Tel Aviv University (IL), Duke University (US), The Kids Research Institute Australia (AU), The University of Western Australia (AU), German Cancer Research Center (DE), University of California, San Francisco (US), Baylor College of Medicine (US), University of Utah (US), Heidelberg University (DE), University of Michigan (US), Sheba Medical Center (IL), Montreal Children's Hospital (CA), Severance Hospital (KR), Great Ormond Street Hospital (GB), Princess Margaret Hospital for Children (AU), Rambam Health Care Campus (IL), Women's and Children's Hospital (AU), McGill University Health Centre (CA), Cancer Institute of New South Wales (AU), Centre Hospitalier Universitaire Sainte-Justine (CA), Copenhagen University Hospital (DK), Rigshospitalet (DK), UNSW Sydney (AU), Humboldt-Universität zu Berlin (DE), NYU Langone Health (US), Children’s Health Queensland Hospital and Health Service (AU), Indo-American Center (US), Seoul National University Children's Hospital (KR), Schneider Children's Medical Center (IL), Center for Cancer and Blood Disorders (US), KK Women's and Children's Hospital (SG), Hopp Children's Cancer Center Heidelberg (DE), NGM Biopharmaceuticals (United States) (US), Sydney Children's Hospital (AU), Princess Máxima Center (NL), University Children's Hospital Zurich (CH), South Australian Health and Medical Research Institute (AU), Great North Children's Hospital (GB), Texas Children's Hospital (US), Sydney Children’s Hospitals Network (AU), Children's Cancer Center (US), C. S. Mott Children's Hospital (US), Yonsei University Health System (KR), Dana-Farber/Boston Children's Cancer and Blood Disorders Center (US), Université Laval (CA), Perth Children's Hospital, Robert H. Lurie Comprehensive Cancer Center of Northwestern University, University College London (GB), The University of Adelaide (AU), Université de Montréal (CA), Freie Universität Berlin (DE), Charité - Universitätsmedizin Berlin (DE), University of Pennsylvania (US), Newcastle University (GB), Philadelphia University (US)
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Neuroblastoma Research and Treatments
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