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Tovorafenib (DAY101)

RAF-altered pediatric low-grade glioma requiring first-line systemic therapy

Also known as TAK-580
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155 sources

Product information and disease descriptionPlace of product in therapyDisease descriptionEpidemiology

Incidence of RAF-altered pediatric low-grade glioma requiring first-line systemic therapy

10 evidence topics · 10 sources

Summary: incidence estimates and the population requiring first-line systemic therapy

No identified publication reports the incidence of RAF-altered pLGG requiring first-line systemic therapy directly. The available components are as follows.

  • Overall incidence, United States: the CBTRUS childhood and adolescent report (2017 to 2021 diagnoses) reports an annual incidence of 0.98 per 100,000 for pilocytic astrocytoma in ages 0 to 19 years and projects 730 new pilocytic astrocytoma cases in 2025. The LOGGIC/FIREFLY-2 design publication cites 1,200 to 1,500 new pLGG cases per year in the United States. Day One Biopharmaceuticals cites an annual incidence of 1.3 to 2.1 per 100,000.
  • Overall incidence, Europe: in Great Britain, the incidence of pilocytic astrocytoma at ages 0 to 14 years was 8.6 per million in 2006 to 2010.
  • RAF-altered fraction: KIAA1549-BRAF fusion was found in 35% and BRAF p.V600E in 17% of profiled tumors in a population-based Toronto cohort. Day One Biopharmaceuticals estimates that approximately 1,100 patients under 25 years of age are newly diagnosed with BRAF-altered pLGG in the United States each year.
  • Fraction requiring nonsurgical therapy: in the UK CCLG CNS9702 population-based cohort, 165 of 639 children (25.8%) started nonsurgical treatment at diagnosis (113 chemotherapy, 52 radiotherapy). In the German HIT-LGG-1996 cohort of 1,031 children, 184 proceeded to nonsurgical treatment at diagnosis and 35.2% ultimately received nonsurgical treatment. In SIOP-LGG 2004, 1,057 of 3,417 registered, previously untreated patients (30.9%) received chemotherapy. Reviews state that up to half of patients require adjuvant therapy.
United States: CBTRUS incidence of pilocytic astrocytoma and glioma in ages 0 to 19 years

“Among CBTRUS specific histopathology groupings, incidence rates were highest for pilocytic astrocytoma (0.98 per 100,000) and tumors of the pituitary (0.98 per 100,000).” (opens the source at this quote in a new tab)

“The most frequently reported histopathology in all ages (0-19 years) was pilocytic astrocytoma (16.3%). Overall, gliomas accounted for 45% of all brain tumors diagnosed in ages 0-19 years.” (opens the source at this quote in a new tab)

“Pilocytic astrocytoma and tumors of the pituitary had the highest number of estimated new cases, with 730 new cases per histopathology expected to be diagnosed in 2025.” (opens the source at this quote in a new tab)

“The median age of glioma diagnosis was 9 years with subtypes ranging from 7 years for pilocytic astrocytoma to 11 years for other low-grade glioma.” (opens the source at this quote in a new tab)

“In children ages 0-3 years, pilocytic astrocytoma tumors had a significant increase in incidence during the entire period (APC: 3.0%; 2.1%, 3.9%).” (opens the source at this quote in a new tab)

United States: registry coding change for pilocytic astrocytoma from 2023

“It should be noted that cases of pilocytic astrocytoma or juvenile pilocytic astrocytoma diagnosed in, or after, 2023 (and therefore not available for analysis until 2026) will no longer be considered malignant (/3), but uncertain (/1); ICD-O-3 code 9421/3 will be reserved for high grade astrocytoma with piloid features.” (opens the source at this quote in a new tab)

United States: annual number of new pLGG cases

“Pediatric low-grade glioma (pLGG) is a heterogeneous group of World Health Organization (WHO) grade 1 and 2 tumors comprising several subgroups and is the most frequent pediatric central nervous system (CNS) tumor diagnosis, with 1200 to 1500 new cases per year in the United States (US)” (opens the source at this quote in a new tab)

United States: company estimates of pLGG and BRAF-altered pLGG incidence

“While pLGG is the most common brain tumor diagnosed, representing approximately 30% of all childhood brain tumors, the annual estimated incidence of pLGG is 1.3 to 2.1 per 100,000 in the United States.” (opens the source at this quote in a new tab)

“Based on incidence results published in academic journals, we estimate that approximately 1,100 patients under the age of 25 are newly diagnosed with BRAF-altered pLGG every year.” (opens the source at this quote in a new tab)

“Potential for tovorafenib, a type-II RAF inhibitor, to be a high-impact targeted therapeutic in pLGG where approximately 70% of tumors are BRAF-altered pLGG in the United States.” (opens the source at this quote in a new tab)

Europe: population-based incidence of pilocytic astrocytoma in Great Britain

“Age-standardised incidence in 2001–10 was 40.1 per million.” (opens the source at this quote in a new tab)

“Between the same two periods, the proportional increase was greater for pilocytic astrocytoma (202%, from 2.9 per million to 8.6 per million) than for astrocytomas of other or unspecified subtype (40%, from 5.8 per million to 8.2 per million)” (opens the source at this quote in a new tab)

“The most frequent single histological type of tumour was pilocytic astrocytoma, which accounted for one half of all astrocytomas and 21% of all tumours.” (opens the source at this quote in a new tab)

“The highest incidence of pilocytic astrocytoma and unspecified optic nerve astrocytoma was at age 1–4 years.” (opens the source at this quote in a new tab)

Europe: proportion of children starting nonsurgical therapy in the UK population-based CNS9702 cohort

“This network registered 80%–86% of the UK cases of childhood LGG registered by the national childhood cancer registry during this time period.” (opens the source at this quote in a new tab)

“Four hundred and seventy-four (74.2%) were initially observed (median age: 7.43 years; Fig. 1). One hundred and sixty-five (25.8%) started nonsurgical treatment (median age: 4.95 years), 113 had chemotherapy (median age: 3.65 years), and 52 had radiotherapy (median age: 9.36 years).” (opens the source at this quote in a new tab)

Europe: proportion of children receiving nonsurgical therapy in the German HIT-LGG-1996 cohort

“Following first surgical intervention in 916 children and radiologic diagnosis in 115 children, 847 patients were observed and 184 proceeded to nonsurgical treatment at diagnosis (1 without exact date).” (opens the source at this quote in a new tab)

“After initial observation, progression occurred in 40.9% of cases within 10 years and indicated nonsurgical therapy in 51.7%.” (opens the source at this quote in a new tab)

“Ultimately, 35.2% of patients in our study received nonsurgical treatment.” (opens the source at this quote in a new tab)

Europe: registrations and chemotherapy use in the SIOP-LGG 2004 study

“3417 previously untreated patients from 118 institutions in 11 countries were registered at the SIOP-LGG 2004 database following the SIOP-LGG treatment strategy.” (opens the source at this quote in a new tab)

“During the trial period, 1057 patients received chemotherapy.” (opens the source at this quote in a new tab)

Proportion requiring therapy beyond surgery by tumor location

“However, with progression-free survival (PFS) at approximately 50%, up to half of patients will require adjuvant therapy.” (opens the source at this quote in a new tab)

“However, many pLGGs arise within structures of the brain that cannot be safely resected without causing substantial morbidity, for example, the optic pathway; midline locations involving the hypothalamus, thalamus, or brainstem; or those intricately associated with motor pathways. Tumors in these locations, in addition to those pLGGs with multiply recurrent or metastatic disease, often require therapy beyond surgery with a few exceptions.” (opens the source at this quote in a new tab)

“hypothalamic-chiasmatic tumours in particular are generally considered unresectable, they present when the children are very young and can threaten vision, endocrine function and require non-surgical therapy” (opens the source at this quote in a new tab)

Directly measured incidence of RAF-altered pLGG requiring first-line systemic therapy

No evidence found.