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
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.
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.The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.