The primary objective of the study was to evaluate the efficacy of VI and VIT regimens, defined as objective response (OR)—complete response (CR) plus partial response (PR)—after 2 cycles. Secondary objectives were progression-free survival (PFS), overall survival (OS), and safety in each arm, and the relative treatment effect of VIT compared to VI in terms of OR, survival, and safety.
The international, randomized (1:1), open-label, phase 2 trial (VIT-0910; NCT01355445) was conducted at 37 centers in 5 countries. Patients ages 6 months to 50 years with RMS were eligible. They could not have had prior irinotecan or temozolomide. A 2015 protocol amendment limited enrollment to patients at relapse and increased the enrollment goal by 40 patients. After the 2015 amendment, patients with refractory disease were no longer eligible.
From January 2012 to April 2018, investigators enrolled 120 patients, 60 on each arm. Two patients in the VI arm were not treated. Patients were a median age of 10.5 years in the VI arm and 12 years in the VIT arm, 92% (VI) and 87% (VIT) had relapsed disease, 8% (VI) and 13% (VIT) had refractory disease, and 55% (VI) and 68% (VIT) had metastatic disease at study entry.
Results
Patients achieved an OR rate of 44% (VIT) and 31% (VI) for the whole population, one-sided P value <.0001. The adjusted odds ratio for the whole population was 0.50, P=.09. PFS was 4.7 months (VIT) and 3.2 months (VI), “a nearly significant reduction in the risk of progression,” Dr. Defachelles noted. Median OS was 15.0 months (VIT) and 10.3 months (VI), which amounted to “a large and significant reduction in the risk of death,” she said. The adjusted hazard ratio was 0.55, P=.006.
Adverse events of grade 3 or higher were more frequent in the VIT arm, with hematologic toxicity the most frequent (81% for VIT, 59% for VI), followed by gastrointestinal adverse events. “VIT was significantly more toxic than VI,” Dr. Defachelles observed, “but the toxicity was manageable.”
“VIT is now the standard treatment in Europe for relapsed rhabdomyosarcoma and will be the control arm in the multiarm, multistage RMS study for relapsed patients,” she said.