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.

Abstract

PURPOSE:

To determine whether the administration of histology-tailored neoadjuvant chemotherapy (HT) was superior to the administration of standard anthracycline plus ifosfamide neoadjuvant chemotherapy (A+I) 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 = 97 [33.8%]; HG-MLPS: n = 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 A+I should remain the regimen to choose whenever neoadjuvant chemotherapy is used in patients with high-risk STS.

• Authors: Alessandro Gronchi, Emanuela Palmerini, Vittorio Quagliuolo, Javier Martin Broto, Antonio Lopez Pousa, Giovanni Grignani, Antonella Brunello, Jean-Yves Blay, Oscar Tendero, Robert Diaz Beveridge, Virginia Ferraresi, Iwona Lugowska, Domenico Franco Merlo, Valeria Fontana, Emanuela Marchesi, Luca Braglia, Davide Maria Donati, Elena Palassini, Giuseppe Bianchi, Andrea Marrari, Carlo Morosi, Silvia Stacchiotti, Silvia Bagué, Jean Michel Coindre, Angelo Paolo Dei Tos, Piero Picci, Paolo Bruzzi, Paolo Giovanni Casali
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 38 Issue 19 Pg. 2178-2186 (07 01 2020) ISSN: 1527-7755 [Electronic] United States
• PMID: 32421444 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Topics

• Adult
• Disease-Free Survival
• Female
• France
• Humans
• Italy
• Male
• Middle Aged
• Neoadjuvant Therapy (methods)
• Poland
• Prospective Studies
• Sarcoma (drug therapy, mortality)
• Soft Tissue Neoplasms (drug therapy, mortality)
• Spain