TY - JOUR
T1 - 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
AU - Gronchi, Alessandro
AU - Palmerini, Emanuela
AU - Quagliuolo, Vittorio
AU - Martin Broto, Javier
AU - Lopez Pousa, Antonio
AU - Grignani, Giovanni
AU - Brunello, Antonella
AU - Blay, Jean-Yves
AU - Tendero, Oscar
AU - Diaz Beveridge, Robert
AU - Ferraresi, Virginia
AU - Lugowska, Iwona
AU - Merlo, Domenico Franco
AU - Fontana, Valeria
AU - Marchesi, Emanuela
AU - Braglia, Luca
AU - Donati, Davide Maria
AU - Palassini, Elena
AU - Bianchi, Giuseppe
AU - Marrari, Andrea
AU - Morosi, Carlo
AU - Stacchiotti, Silvia
AU - Bague, Silvia
AU - Coindre, Jean Michel
AU - Dei Tos, Angelo Paolo
AU - Picci, Piero
AU - Bruzzi, Paolo
AU - Casali, Paolo Giovanni
PY - 2020/7/1
Y1 - 2020/7/1
N2 - 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.
AB - 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.
U2 - 10.1200/JCO.19.03289
DO - 10.1200/JCO.19.03289
M3 - Article
VL - 38
SP - 2178
EP - 2186
JO - J. Clin. Oncol.
JF - J. Clin. Oncol.
SN - 0732-183X
IS - 19
ER -