As reported in the Journal of Clinical Oncology by Alessandro Gronchi, MD, and colleagues, final results of a phase III trial conducted by the Italian, French, and Polish Sarcoma Groups showed no disease-free or overall survival benefit with use of histology-tailored vs standard anthracycline/ifosfamide neoadjuvant chemotherapy in patients with high-risk soft-tissue sarcoma.
Alessandro Gronchi, MD
Study Details
In the open-label trial, 287 patients from sites in Italy, Spain, France, and Poland with localized high-risk disease (grade 3, ≥ 5 cm) of an extremity or trunk wall belonging to one of five histologic subtypes were randomly assigned between May 2011 and May 2016 to receive standard anthracycline/ifosfamide neoadjuvant therapy (n = 145) or histology-tailored regimens (n = 142).
The histologic subtypes consisted of high-grade myxoid liposarcoma (n = 65), leiomyosarcoma (n =28), synovial sarcoma (n = 70), malignant peripheral nerve sheath tumor (n = 27), and undifferentiated pleomorphic sarcoma (n = 97). The histology-tailored regimens consisted of trabectedin for high-grade myxoid liposarcoma, gemcitabine/dacarbazine for leiomyosarcoma, high-dose prolonged-infusion ifosfamide for synovial sarcoma, etoposide/ifosfamide for malignant peripheral nerve sheath tumor, and gemcitabine/docetaxel for undifferentiated pleomorphic sarcoma.
Primary and secondary endpoints were disease-free survival and overall survival in the intent-to-treat populations.
Key Findings
The study was terminated early for futility, after the third prespecified futility analysis at a median follow-up of 1 year and after enrollment of 287 patients of the target population of 350.
In total, 281 patients (97.9%) underwent planned surgery.
At final analysis, with median follow-up of 52 months, the projected 5-year probabilities for disease-free survival were 47% (95% confidence interval [CI] = 0.38–0.57) in the histology-tailored group vs 55% (95% CI = 0.46–0.63) in the anthracycline/ifosfamide group (hazard ratio [HR] = 1.23, P = .32). The projected 5-year probabilities for overall survival were 0.66 (95% CI = 0.57–0.75) in the histology-tailored group vs 0.76 (95% CI = 0.67–0.84) in the anthracycline/ifosfamide group (HR = 1.77, P = .02).
“In a population of patients with localized high-risk soft-tissue sarcoma, histology-tailored neoadjuvant chemotherapy was not associated with…better disease-free survival or overall survival, suggesting that anthracycline/ifosfamide should remain the regimen to choose whenever neoadjuvant chemotherapy is used in patients with high-risk soft-tissue sarcoma.”— Alessandro Gronchi, MD
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Among 230 patients evaluable for response on RECIST version 1.1 criteria, 13.6% of patients in the anthracycline/ifosfamide group and 6.2% of patients in the histology-tailored group had partial responses (no complete responses were observed), with 79.5% and 80.5% having stable disease.
No treatment-related deaths were observed.
The investigators concluded, “In a population of patients with localized high-risk soft-tissue sarcoma, histology-tailored neoadjuvant chemotherapy was not associated with…better disease-free survival or overall survival, suggesting that anthracycline/ifosfamide should remain the regimen to choose whenever neoadjuvant chemotherapy is used in patients with high-risk soft-tissue sarcoma.”
Dr. Gronchi, of the Department of Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was funded by a grant from the European Union, PharmaMar, and others. For full disclosures of the study authors, visit ascopubs.org.
