KEY TAKEAWAYS
- The phase I trial aimed to evaluate the toxicity and PK of anlotinib in pediatric sarcoma pts.
- Pediatric sarcoma pts received oral anlotinib once daily for 2 weeks on/off.
- The study found that anlotinib was well tolerated in pediatric sarcoma pts.
Anlotinib is a potent oral multi-kinase inhibitor that blocks VEGF and FGFR signaling. Researchers aimed to evaluate the toxicity and pharmacokinetics (PK) of anlotinib in pediatric sarcoma patients(pts).
Pediatric sarcoma pts aged 5-18 with high-risk, recurrent, or refractory cases were divided into two groups, cohort A (<35 kg) and cohort B (≥35 kg). Anlotinib was administered orally once daily on a 2-weeks-on, off schedule until specific endpoints were reached (disease progression, death, unacceptable toxicity, or consent withdrawal). Cohort A received a fixed 8 mg dose, while cohort B underwent dose evaluation (8mg, 10mg, 12mg) following a “3 + 3” design.
Of the 34 pts enrolled, 19 (55.9%) were evaluated for efficacy, and their median age was 12 years (range: 5-18). The primary eligible subtype was rhabdomyosarcoma (23.5%). In cohort A (8 mg dose), 2 out of 15 pts experienced dose-limiting toxicity, which included grade 3 hematuria and grade 3 hand-foot syndrome. Grade 3 treatment-related adverse events (AEs) encompassed neutropenia (8.8%), hand-foot syndrome (5.9%), headache (2.9%), hematuria (2.9%), hypertension (2.9%), and hyperbilirubinemia (2.9%). The most common AEs were grade 1 or 2 hypothyroidism (58.8%) and abdominal pain (55.9%). Stable disease was the best response for 63.2% (12 out of 19) of pts, with 7 pts receiving six or more cycles. Age did not significantly impact drug exposure per unit body surface area dose, and patients younger than 12 exhibited faster elimination.
The study found that anlotinib was well tolerated in pediatric sarcoma pts, with RP2D of 8 mg for <35 kg and 12 mg for ≥35 kg.
Source: https://ascopubs.org/doi/abs/10.1200/JCO.2023.41.16_suppl.e23538
Clinical Trial: https://www.clinicaltrials.gov/study/NCT04659733
Suying Lu, Juan Wang, Feifei Sun, Junting Huang, Jia Zhu, Ruiqing Cai, Zijun Zhen, and Yizhuo Zhang. DOI: 10.1200/JCO.2023.41.16_suppl.e23538 Journal of Clinical Oncology 41, no. 16_suppl (June 01, 2023) e23538-e23538.
