Investigators conducted an open-label, randomized, multi-center phase 2 study of VIT and vincristine with irinotecan without temozolomide that included 120 patients from 37 European centers.
The results of a phase 2 trial examining combination vincristine and irinotecan with or without temozolomide in children and adults with refractory or relapsed rhabdomyosarcoma (RMS) were presented at the American Society of Clinical Oncology (ASCO) 2019 Annual Meeting.
After analyses, the international team of investigators found that the addition of temozolomide to vincristine with irinotecan (VIT) improves progression-free survival (PFS) and overall survival (OS) in patients with relapsed/refractory RMS.
Investigators carried out an open-label, randomized, multi-center phase 2 study of VIT and vincristine with irinotecan without temozolomide (VI) that included 120 patients from 37 European centers from March 2012 to April 2018 with refractory or relapsed RMS. The trial evaluated the efficacy and safety of VI and VIT in patients between .5 and 50 years old. Patients were randomized at a 1:1 ratio, 60 were randomized into the VIT group and 60 into the VI group.
Patients received vincristine 1.5mg/md2 d1, d8, irinotecan 50mg/m2 d1-d5 with or without temozolomide 125mg/m2 d1-d5 (150 mg/m2 from cycle 2 if no toxicity greater than grade 2). Investigators gave patients 21-day cycles until progression/unacceptable toxicity.
The primary endpoint of the study was centrally reviewed objective response rate (ORR) after 2 curls (primary lesion, WHO response criteria: metastatic sites, RECIST 1.1). Secondary endpoints for the study included OFS, OS, and adverse events.
Authors noted that, initially, a Simon 2-stage design was used to analyze separately 40 patients per arm—this was changed and the sample size was increased to 120. A comparison between arms adjusting for compounding factors was added to the statistical plan.
Median age of patients was 11 years and 89% of patients had relapsed RMS. The ORR was 24 out of 55 (44%) for the VIT group compared to 18 of 58 (31%) in the VI group (adjusted odds ratio= 0.50, 95%CI: 0.22 - 1.12, P= .09). Additionally, the VIT group achieved significantly better PFS (Adjusted HR= 0.65, 95% Cl: 0.43 - 0.97, P= .036) and OS (HR= 0.53, 95%CI: 0.33 - 0.83, P= .005) compared to the VI group.
PFS and OS results were similar when comparing only relapsed patients. Adverse events greater than grade 3 were more frequent in the VIT group, but only hematological toxicity was significantly increased (81% for VIT, 59% for VI, odds ratio=1.36, 95%CI, 1.06-1.76, P=0.02).
This study, “International Randomized Phase II Trial of the Combination of Vincristine and Irinotecan With or Without Temozolomide in Children and Adults With Refractory or Relapsed Rhabdomyosarcoma,” was presented at ASCO 2019.