mTOR inhibitor everolimus versus conventional chemotherapy in pediatric low-grade gliomas

Standard chemotherapy in pediatric low-grade gliomas (pLGG) has limited efficacy and substantial toxicity, while clinical data on everolimus are lacking. This study compared the efficacy of everolimus and traditional chemotherapy in patients with pLGG, and evaluated the treatment response, survival, and the frequency and severity of adverse events. This single-center retrospective cohort study analyzed 279 patients with pathologically confirmed World Health Organization (WHO) grade 1-2 pLGG (Jan 2014-Jan 2021): 126 received everolimus and 153 received standard carboplatin-vincristine (CV) chemotherapy. The primary efficacy endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR), and clinical benefit rate (CBR). In the optic pathway glioma subgroup, visual function changes were assessed using the pediatric eye questionnaire (PedEyeQ) scale along with objective ophthalmic indicators including best-corrected visual acuity, visual field assessment, and optic nerve atrophy grading. Safety was evaluated by recording adverse events according to the CTCAE v5.0 criteria, with exposure-adjusted rates calculated per 100 patient-years to account for differential treatment duration, and long-term pediatric safety was assessed through 5-year follow-up of growth, bone metabolism, and endocrine function. The follow-up period was 5 years. The median PFS was 49.00 months (95% CI: 37.00-55.00) in the everolimus group and 41.00 months (95% CI: 28.00-55.00) in the CV group, with no significant difference (Log-rank χ²=0.162, P=0.688) and a hazard ratio (HR) of 0.939 (95% CI: 0.684-1.288). OS did not differ significantly between the everolimus and CV groups (Log-rank χ²=0.423, P=0.515), with an HR of 0.778 (95% CI: 0.365-1.662). No significant differences were observed in ORR, DCR, or CBR (all P>0.05). In the optic pathway glioma subgroup, the 5-year PedEyeQ scores were significantly higher in the everolimus group than in the CV group (P<0.001), and objective ophthalmic assessments consistently demonstrated better visual preservation with everolimus. In terms of safety, the incidence of grade 3-4 adverse events was significantly lower in the everolimus group than in the CV group (22.22% vs. 44.44%, P<0.001). The incidence of hematologic toxicity (26.19% vs. 52.94%, P<0.001) was significantly lower in the everolimus group; non-hematologic toxicities, including nausea, vomiting, and alopecia, were also significantly lower in the everolimus group. The most common adverse events in the everolimus group were oral mucositis (49.21%), hyperlipidemia (38.10%), and rash (25.40%), most of which were grade 1-2 and manageable. Exposure-adjusted safety analyses confirmed these findings, and 5-year follow-up showed no significant between-group differences in growth, bone metabolism, or endocrine function. For pLGG patients, everolimus is comparable to carboplatin in terms of efficacy, but has significantly better safety and fewer serious adverse events, along with potential advantages in visual function preservation and reduced healthcare resource utilization.