Adding temozolomide to a combination of vincristine and irinotecan improved overall survival in patients with relapsed or refractory rhabdomyosarcoma (RMS), according to a phase 2 study published in the Journal of Clinical Oncology.

The VIT-0910 trial ( Identifier: NCT01355445) enrolled 120 patients from 37 centers in 5 countries. At baseline, patients had a median age of 11 years (range, 9.1 months to 45 years), and 89% of them had relapsed RMS.

Patients were randomly assigned 1:1 to receive temozolomide plus vincristine-irinotecan (VIT) or vincristine-irinotecan (VI). Patients received a median of 6 cycles (range, 1-18) of VIT and a median of 4 cycles (range, 1-26) of VI. 

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There was no significant difference between the treatment arms in objective response rate (ORR) after 2 cycles of treatment. The ORR after 2 cycles was 44% in the VIT arm and 31% in the VI arm (adjusted odds ratio [aOR], 0.50; 95% CI, 0.22-1.12; P =.09).

However, the best ORR over the treatment period was significantly better in the VIT arm. The best ORR was 57% in the VIT arm and 38% in the VI arm (aOR, 0.40; 95% CI, 0.18-0.88; P =.023).

There was no significant between-arm difference in progression-free survival, but overall survival was significantly better in the VIT arm.

The median progression-free survival was 4.7 months in the VIT arm and 3.2 months in the VI arm (adjusted hazard ratio [aHR], 0.68; 95% CI, 0.46-1.01; P =.059). 

The median overall survival was 15.0 months and 10.3 months, respectively (aHR, 0.55; 95% CI, 0.35-0.84; P =.006).

Grade 3 or higher adverse events (AEs) were observed more frequently in the VIT arm than in the VI arm — 98% and 78%, respectively (P =.009). The same was true for grade 3 or higher treatment-related AEs — 93% and 69%, respectively (P =.002).

The rate of treatment-related serious AEs was significantly higher in the VIT arm than in the VI arm — 38% and 19%, respectively (P =.023). The same was true for severe hematologic toxicity — 81% and 61%, respectively (P =.025).

No treatment-related deaths were reported in either arm.

“The addition of temozolomide to VI improved chemotherapy efficacy for patients with relapsed RMS, with manageable increase in toxicity,” the study authors wrote. “The study has defined the combination of vincristine, irinotecan, and temozolomide as a new standard chemotherapy treatment option for relapsed RMS.” 

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Defachelles AS, Bogart E, Casanova M, et al. Randomized phase II trial of vincristine-irinotecan with or without temozolomide, in children and adults with relapsed or refractory rhabdomyosarcoma: A European paediatric Soft Tissue Sarcoma Study Group and Innovative Therapies for Children with Cancer trial. J Clin Oncol. Published online August 03, 2021. doi: 10.1200/JCO.21.00124