In the European phase II VIT-091 trial, researchers examined the efficacy of the combination of vincristine and irinotecan with or without the addition of temozolomide in children and adults with relapsed or refractory rhabdomyosarcoma. Their results were presented by Defachelles et al at the 2019 ASCO Annual Meeting (Abstract 10000).
Patients were recruited at 37 European centers from 2012 to 2018. The median age was 11 years (range = 0.75–46 years), and 89% of patients had relapsed rhabdomyosarcoma.
Patients received vincristine at 1.5 mg/m2 on days 1 and 8 and irinotecan at 50 mg/m2 on days 1 to 5 of 21-day cycles, then were randomly assigned to receive either no temozolomide or temozolomide at 125 mg/m² on days 1 to 5 (150 mg/m² from cycle 2 if no toxicity > grade 2). Treatment was given in 21-day cycles until disease progression or unacceptable toxicity.
The primary endpoint was centrally reviewed objective response rate after two cycles (primary lesion responses were assessed by World Health Organization criteria; metastatic site responses were assessed by Response Evaluation Criteria in Solid Tumors, version 1.1). After amendment of the study design, the trial sample size was increased to 120, and a comparison between arms, adjusted for confounding factors, was added to the statistical plan.
The objective response rate was 44% for vincristine/irinotecan/temozolomide vs 31% for vincristine/irinotecan (adjusted odds ratio = 0.50, 95% confidence interval [CI] = 0.22–1.12; P = .09). The vincristine/irinotecan/temozolomide arm achieved better progression-free survival (adjusted hazard ratio [HR] = 0.65, 95% Cl = 0.43–0.97; P = .036) and overall survival (HR = 0.53, 95% CI = 0.33–0.83; P = .005) compared to vincristine/irinotecan. Progression-free and overall survival results were similar when only relapsed patients were included.
Adverse events of at least grade 3 were more frequent in the vincristine/irinotecan/temozolomide arm compared to vincristine/irinotecan, but only hematologic toxicity was significantly increased (81% for vincristine/irinotecan/temozolomid vs 59% for vincristine/irinotecan).
The authors concluded, “The addition of temozolomide to vincristine/irinotecan improves [progression-free and overall survival] of patients with relapsed [or] refractory rhabdomyosarcoma. [Vincristine/irinotecan/temozolomide] is now standard treatment for relapsed rhabdomyosarcoma in Europe.”
Disclosure: For full disclosures of the study authors, visit coi.asco.org.
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