Weekly Vinblastine in Chemotherapy-Naive Children With Progressive Low-Grade Glioma


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In a phase II Canadian Pediatric Brain Tumor Consortium Study reported in the Journal of Clinical Oncology, Lassaletta et al found that vinblastine monotherapy was associated with response or stable disease in most children with chemotherapy-naive low-grade glioma. Vinblastine monotherapy has shown promising activity and a good toxicity profile in pediatric low-grade glioma after failure of initial chemotherapy and/or radiation therapy.

Eric Bouffet, MD, of The Hospital for Sick Children, Toronto, Ontario, Canada, is the corresponding author of the Journal of Clinical Oncology article.

The study involved 54 patients aged < 18 years (median = 8 years) with unresectable or progressive pediatric low-grade glioma. Vinblastine was given intravenously once a week at 6 mg/m2 over 70 weeks. Chiasmatic/hypothalamic tumors were present in 55.5% of patients, and neurofibromatosis type 1 was present in 24.1%. Pilocytic astrocytoma was the most common histology (46.3%). Diagnosis was made using radiologic criteria alone in 31.5%.

Responses

On central review, response was observed in 25.9% of patients, with disease stabilization observed in 87.0% (complete response in 1 patient, partial response in 9, minor response in 4, and stable disease in 34). Visual improvement was observed in 20% of patients with optic pathway glioma. Among all patients, 5-year overall survival was 94.4%, and 5-year progression-free survival was 53.2%. Five-year progression-free survival was better in patients with vs without neurofibromatosis type 1 (85.1% vs 42.0%, P = .012). Age < 3 years or > 10 years was not associated with poorer outcome.

Among 29 samples tested, 13 (45%) were positive for BRAF fusion; in patients with BRAF fusion, 5-year rates were 100% for overall survival and 56.2% for progression-free survival, with rates not differing from those in patients without BRAF fusion (87.5% and 44.9%). BRAF V600E mutation was found in 3 of 31 samples: disease progression occurred in 1 patient, stable disease occurred in 1 patient, and partial response was achieved in 1 patient. Overall, at a median follow-up of 5 years, 31 patients had not required further therapy.

Toxicity

Treatment was well tolerated. The most common grade 3 and 4 adverse events considered probably related to treatment were grade 3 (40.7%) and 4 (35.2%) neutropenia, grade 3 febrile neutropenia (11.1%), grade 3 infection (9.3%), and grade 3 anemia (3.7%). No adverse effect on quality of life was observed.

The investigators concluded: “Vinblastine administered once per week is well tolerated in children with treatment naive [pediatric low-grade glioma]. Overall survival and [progression-free survival] are comparable to current therapies, with a favorable toxicity profile and a maintained quality of life.”

The study was supported by a grant from the Ontario Institute for Cancer Research and others.

Lassaletta A, et al: J Clin Oncol. August 29, 2016 (early release online).



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