Early results from Children's Oncology Group (COG) ARST0431: Intensive multidrug therapy for patients with metastatic rhabdomyosarcoma (RMS).

Abstract

9503 Background: The outcome for patients with metastatic RMS has remained approximately 30% survival for several decades. The COG phase 3 trial, ARST0431 aimed to 1) improve early disease control using interval compressed therapy of known active agents: vincristine, doxorubicin, and cyclophosphamide (VDC) alternating with ifosfamide, etoposide (IE) and 2) to determine the feasibility and toxicity of vincristine/irinotecan (VI) given concurrently with radiation therapy. Methods: We conducted a phase 3, single arm study. Previously untreated patients <50 yrs with metastatic RMS and adequate organ function were eligible for enrollment. Patients received 54 wks of therapy: blocks of therapy with VI (wks 1-6, 20-25, 47-52), interval compression with VDC/IE (wks 7-19 and 26-34) and vincristine, actinomycin D and cyclophosphamide (VAC) (wks 38-46). Radiation therapy occurred at wk 20-25 (primary) but was also permitted at wk 1-6 (for intracranial or paraspinal extension) and wk 47-52 (for extensive metastatic sites). Results: The study enrolled 109 eligible pts from 7/2006 and 6/2008. 20 pts received irinotecan on the protracted daily × 5 for two consecutive wks schedule before a protocol amendment, and 89 pts received irinotecan on the shorter daily × 5 schedule. The majority of pts were between ages 10-20 (56%), male (55%), with alveolar histology (59%), primary tumors ≥5cm (80%) and had regional lymph nodal involvement (60%). Toxicity was comparable to the prior COG study with VI and VAC, D9802, as was the early response rate (RR) after VI for 6 wks (CR 7%, PR 57%). The early response rate was also similar by histology (RR for embyronal RMS: 58%; alveolar RMS: 66%). At 18 mos, the failure-free survival (FFS) and OS rates are 66% (55-75%, 95% CI) and 80% (70-87%, 95% CI), respectively. A comparable pooled analysis of metastatic RMS pts from European and North American clinical trials (J Clin Oncol 2008;26:2384-9) had an 18 mo FFS of 41% for all pts, and 45% when restricted to North American pts only. Conclusions: Pts with metastatic RMS treated on ARST0431 experienced similar toxicity compared to prior COG trials. Early outcome data appear promising, with a FFS at 18 mos 20% higher than prior studies. Longer follow up is required. No significant financial relationships to disclose.