Product information and disease description Place of product in therapy Disease description Burden of RAF-altered pediatric low-grade glioma requiring first-line systemic therapy

Humanistic burden and health-related quality of life

14 evidence topics · 10 sources

Summary: health-related quality of life in pLGG

No study was identified that reports health-related quality of life (HRQoL) specifically in RAF-altered pLGG at the start of first-line systemic therapy, and no published patient-reported outcome (PRO) comparison of first-line chemotherapy versus a MAPK pathway inhibitor was located. Available evidence comes from survivorship cohorts, optic pathway glioma (OPG) cohorts, single-arm chemotherapy trials, and HTA testimony.

In a Mayo Clinic cohort of 121 survivors (median follow-up 21.9 years), mean EORTC QLQ-C30 global QoL was 78, compared with 76.4 in a healthy adult reference population; post-operative radiation, deep tumor location, and recurrence were associated with poorer HRQoL, and participants with recurrence reported more financial problems. In a German survey of 49 survivors, survivors rated their QoL higher than peers, but their parents did not. Among 36 children aged 10 years or younger with OPG, parent-proxy vision-specific QoL was lower with greater vision loss. In a Canadian phase 2 trial of weekly vinblastine in 54 chemotherapy-naive children, QoL was reported as not affected during 70 weeks of intravenous treatment. The ongoing phase 3 LOGGIC/FIREFLY-2 trial is collecting PedsQL-Core, PedsQL-Cancer, and PROMIS measures in both arms. In the NICE appraisal of dabrafenib plus trametinib (TA977), patient experts described regular hospital travel, costs, and time commitments with current treatments, and no child-specific utility values were identified; the committee judged that adult utility decrements likely underestimate the HRQoL loss in children.

Caregiver burden is documented for pediatric brain tumors generally: 85% of 40 caregivers of children newly hospitalized with a brain tumor rated distress 5 or greater on a 0 to 10 scale, and in a five-site matched study of 301 caregivers of brain tumor survivors 1 to 5 years after treatment, mothers reported higher caregiver burden, including financial impact, than mothers of comparison youth.

Long-term survivors: EORTC QLQ-C30 and QLQ-BN20 at a median of 21.9 years

“QOL of 121 patients with a diagnosis of LGG from the Mayo Clinic were assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-C30 for cancer in general) and (EORTC QLQ-BN20 specific for brain tumors).” (opens the source at this quote in a new tab)
“Median follow-up was 21.9 years for the participants. Median age at diagnosis was 11.8 years and at assessment was 33 years. Mean (standard deviation) global QOL score for the study was 78 (18) and 76.4 (22.8) in a reference population of healthy adults.” (opens the source at this quote in a new tab)
“Patients with tumor recurrence reported lower role functioning (p=0.016), social functioning (p=0.040), and more financial problems (p=0.029) compared to their counterparts.” (opens the source at this quote in a new tab)
“In the multivariable analysis, radiation therapy remained an independent predictor of physical and role functioning as well as symptoms related to brain tumors like visual disorders and motor dysfunction.” (opens the source at this quote in a new tab)
“The following tumor and treatment related factors were most consistently associated with poorer QOL: CNS tumor location, post-operative radiation, and tumor recurrence.” (opens the source at this quote in a new tab)

Long-term survivors: self-report versus parent report (KINDL)

“We surveyed 49 survivors and their parents (KINDL questionnaire).” (opens the source at this quote in a new tab)
“Despite tumor and treatment-associated morbidity, survivors (25 boys and 24 girls, median age at diagnosis 7.8 years), but not their parents, rated their total quality of life higher than their peers. Although all survivors had some late morbidity, half of them were able to conduct their daily lives without restriction.” (opens the source at this quote in a new tab)
“These results reflect survivors' effective coping mechanisms and underscore the difficulties of assessing quality of life in pediatric populations.” (opens the source at this quote in a new tab)

Optic pathway glioma: vision-specific quality of life by degree of vision loss

“Vision specific QOL was assessed by parent proxy using the Children’s Visual Function Questionnaire (CVFQ), and scores were analyzed according to magnitude of visual acuity (VA) loss and presence of visual field (VF) loss. Thirty-six subjects completed the study (53% female) with median age of 4.6 years.” (opens the source at this quote in a new tab)
“Lower Competence scores were noted in participants with more profound vision loss (P < .05), reflecting a decreased ability to complete activities of daily living (e.g. feeding, grooming).” (opens the source at this quote in a new tab)
“Children with two visually impaired eyes were rated as having greater difficulty with social interactions and pleasurable activities (Personality subscale, p=.039) compared to those with only one impaired eye.” (opens the source at this quote in a new tab)

Quality of life during first-line intravenous chemotherapy: weekly vinblastine

“Vinblastine was administered once per week at a dose of 6 mg/m2 intravenously over a period of 70 weeks. Vision, quality of life, neurofibromatosis type 1 (NF1) status, and BRAF mutation/fusion status were also determined and correlated with outcome.” (opens the source at this quote in a new tab)
“Treatment was well tolerated, and quality of life was not affected during treatment.” (opens the source at this quote in a new tab)

LOGGIC/FIREFLY-2: planned patient-reported outcome comparison of tovorafenib versus chemotherapy

“Patient-reported outcomes (PRO) assessments: comparison of changes in quality of life (QoL) and health utilities measures between study arms using the Pediatrics Quality of Life™-Core Module (PedsQL-Core), Pediatrics Quality of Life™-Cancer (PedsQL-Cancer), and Patient-Reported Outcomes Measurement Information System (PROMIS ® ) assessment” (opens the source at this quote in a new tab)
“PedsQL-Core, PedsQL-Cancer and PROMIS ® are being assessed at Screening, every 52 weeks from week 5 to end of treatment, and at year 5 as part of the LTFU.” (opens the source at this quote in a new tab)

Patient and caregiver experience of current treatment and utility values: NICE appraisal of dabrafenib plus trametinib

“The patient experts also explained that currently available treatments need regular travel to hospital, incur significant costs and need a substantial time commitment.” (opens the source at this quote in a new tab)
“They highlighted that the toxicity associated with conventional chemotherapy can lead to people with glioma and their caregivers choosing to stop treatment.” (opens the source at this quote in a new tab)
“The company's systematic review was unable to identify utility values for children and young people with glioma.” (opens the source at this quote in a new tab)
“The committee considered that the adult values likely underestimate the utility decrements that would be seen in children and young people.” (opens the source at this quote in a new tab)
“The committee noted the benefits associated with better school attendance and increased socialising that would result from fewer visits to the hospital which would not be captured in adult utility values” (opens the source at this quote in a new tab)

Caregiver distress at diagnosis of a pediatric brain tumor

“Forty primary caregivers were enrolled (of 49 eligible), with the patient age ranging from newborn to 17 years (mean 7.7 years).” (opens the source at this quote in a new tab)
“Mean and median DT scores were 7.2 (SD 2.6) and 7, respectively. However, 12 (30%) rated their distress 10/10, and 85% rated distress 5 or greater.” (opens the source at this quote in a new tab)
“Families of children with newly diagnosed brain tumors experience high levels of distress and psychosocial risk.” (opens the source at this quote in a new tab)

Caregiver burden in survivorship: caregivers of pediatric brain tumor survivors versus matched comparison caregivers

“As part of a five-site study, we utilized a matched-sample design to evaluate psychosocial functioning of 301 caregivers of 189 PBTS (ages 8-15) who were 1-5 years post-treatment, and 286 caregivers of 187 comparison youth matched for sex, race, and age.” (opens the source at this quote in a new tab)
“Caregivers of PBTS reported similar levels of psychological symptoms to caregivers of comparison youth. Mothers of PBTS mothers reported higher caregiver burden and lower perceptions of social support than mothers of comparison youth. Low SES exacerbated group differences in caregiver burden.” (opens the source at this quote in a new tab)
“Results demonstrated a significant main effect of group status on all subscales, such that mothers of PBTS reported higher levels of financial impact, disruption of planning, caretaker burden, familial burden, and significantly lower levels of coping than mothers of comparison youth.” (opens the source at this quote in a new tab)

HRQoL in RAF-altered pLGG before the start of first-line therapy

No evidence found.

Parent-proxy global health and fatigue during first-line dabrafenib plus trametinib versus chemotherapy

“The difference in the overall least-squares means of scores between the trial groups for global health and fatigue favored dabrafenib plus trametinib over chemotherapy at all scheduled time points” (opens the source at this quote in a new tab)
“Outcomes on the pain subscale were similar in the two groups.” (opens the source at this quote in a new tab)
“The clinical benefit of dabrafenib plus trametinib as compared with chemotherapy is further supported by greater improvements in visual acuity and global health.” (opens the source at this quote in a new tab)

Domains in which survivor self-report differed from the reference population

“Thirty-three patients age 11-17 years old were included in the self-evaluated quality of life analysis compared with published norms for this age group (Fig. 1)” (opens the source at this quote in a new tab)
“They rated their total quality of life, physical well-being, and self-esteem significantly higher than their healthy peers (p<0.05).” (opens the source at this quote in a new tab)

Psychological and social late effects and the state of quality of life evidence

“Pediatric LGG patients have shown increased risk as late effects for social difficulties and psychological problems (e.g., anxiety 19%, depression 15%, fatigue, behavioral problems 13%), even without additional treatment with chemo- and radiotherapy” (opens the source at this quote in a new tab)
“Quality of life is gaining attention in LGG, but its evaluation still shows inconsistent results.” (opens the source at this quote in a new tab)

Fatigue and adaptive behavior after treatment

“For children, fatigue after a brain tumor still increases up to 8 years after diagnosis.” (opens the source at this quote in a new tab)
“Adaptive behavior after LGG, measured via the Vineland adaptive behavior scale, is decreased for communication (written skills) and the subdomain gross motor skills. These issues are worse in children with younger age at diagnosis and/or chemotherapy. Residual disease was associated with poorer total adaptive behavior” (opens the source at this quote in a new tab)

Divergent quality of life findings across instruments and the limits of the evidence base

“Sixty-one percent of the patients had impairments (e.g., epilepsy, hormone deficiencies, and motor, visual, sensory, and auditory deficits). Unlike the findings in our study, the Aarsen group reported reduced quality of life for all domains of the TACQOL questionnaire, except in the emotions domain.” (opens the source at this quote in a new tab)
“All four LGG quality of life studies to date have limitations inherent to cross-sectional, single-institution studies. Small sample sizes, of which ours is the largest, decrease the generalizability of the results, reduce the power of the statistical analysis, and increase the chance that differences and correlations within the data may fail to reach a level of significance.” (opens the source at this quote in a new tab)