Neoadjuvant Chemotherapy In High-Risk Soft Tissue Sarcomas: Final Results Of A Randomized Trial From Italian (Isg), Spanish (Geis), French (Fsg), And Polish (Psg) Sarcoma Groups

PURPOSE To determine whether the administration of histology-tailored neoadjuvant chemotherapy (HT) was superior to the administration of standard anthracycline plus ifosfamide neoadjuvant chemotherapy (A1I) in high-risk soft tissue sarcoma (STS) of an extremity or the trunk wall.PATIENTS AND METHODS This was a randomized, open-label, phase III trial. Patients had localized high-risk STS (grade 3; size, >= 5 cm) of an extremity or trunk wall, belonging to one of the following five histologic subtypes: high-grade myxoid liposarcoma (HG-MLPS); leiomyosarcoma (LMS), synovial sarcoma (SS), malignant peripheral nerve sheath tumor (MPNST), and undifferentiated pleomorphic sarcoma (UPS). Patients were randomly assigned in a 1:1 ratio to receive three cycles of A+I or HT. The HT regimens were as follows: trabectedin in HG-MLPS; gemcitabine plus dacarbazine in LMS; high-dose prolonged-infusion ifosfamide in SS; etoposide plus ifosfamide in MPNST; and gemcitabine plus docetaxel in UPS. Primary and secondary end points were disease-free survival (DFS) and overall survival (OS), estimated using the Kaplan-Meier method and compared using Cox models adjusted for treatment and stratification factors. The study is registered at ClinicalTrials.gov (identifier NCT01710176).RESULTS Between May 2011 and May 2016, 287 patients (UPS: n 5 97 [33.8%]; HG-MLPS: n 5 65 [22.6%]; SS: n=70 [24.4%]; MPNST: n=27 [9.4%]; and LMS: n=28 [9.8%]) were randomly assigned to either A+I or HT. At the final analysis, with a median follow-up of 52 months, the projected DFS and OS probabilities were 0.55 and 0.47 (log-rank P = .323) and 0.76 and 0.66 (log-rank P = .018) at 60 months in the A+I arm and HT arm, respectively. No treatment-related deaths were observed.CONCLUSION In a population of patients with localized high-risk STS, HT was not associated with a better DFS or OS, suggesting that A1I should remain the regimen to choose whenever neoadjuvant chemotherapy is used in patients with high-risk STS. (C) 2020 by American Society of Clinical Oncology.