ESMO 2016: Significant Survival Gains From Neoadjuvant Chemotherapy for High-Risk Soft-Tissue Sarcoma

Key Points

  • After a median follow-up of 12.3 months, patients randomized to epirubicin plus ifosfamide showed significantly higher probability of relapse-free survival at 46 months compared to patients randomized to a histology-driven regiment.
  • The patients randomized to epirubicin plus ifosfamide also showed a higher probability of overall survival.
  • While the study failed to show any benefit from histologically tailored regimens, subgroup analysis did suggest that patients with high-grade myxoid liposarcoma who were treated with trabectedin had similar progression-free and overall survival to those treated with epirubicin plus ifosfamide.

Neoadjuvant chemotherapy with an anthracycline plus ifosfamide was associated with significant survival gains in patients with soft-tissue sarcoma of the trunk or extremities who are at high-risk of recurrence, in an interim analysis that led to the early discontinuation of a trial presented by Gronchi et al at the European Society for Medical Oncology (ESMO) 2016 Congress in Copenhagen (Abstract LBA6_PR).

The study compared this chemotherapy with tailoring chemotherapy regimens to histology subtypes.

“The benefit of adjuvant chemotherapy in soft-tissue sarcoma has been debated a lot over recent years because of contradictory study outcomes,” said principal investigator Alessandro Gronchi, MD, Chair of the Sarcoma Surgery at the National Cancer Institute, Milan, Italy.

Study Details

In this multicenter study, researchers recruited 287 patients with high-risk soft-tissue sarcoma of the trunk or extremities, from five histologic subtypes that represent around 80% of all soft-tissue sarcomas arising in an extremity or trunk wall.

Patients were randomized 1:1 either to three cycles of epirubicin (120 mg/m2) plus ifosfamide (9 g/m2), or three cycles of one of five histologically tailored regimens: gemcitabine plus docetaxel in undifferentiated pleomorphic sarcoma; trabectedin in high-grade myxoid liposarcoma; high-dose prolonged-infusion ifosfamide in synovial sarcoma; etoposide plus ifosfamide in malignant peripheral nerve sheath tumors; or gemcitabine plus dacarbazine in leiomyosarcoma. All regimens were given preoperatively.

Key Findings

After a median follow-up of 12.3 months, patients randomized to epirubicin plus ifosfamide showed significantly higher probability of relapse-free survival at 46 months compared to patients randomized to a histology-driven regiment (0.62 vs 0.38, = .004), and of overall survival (0.89 vs 0.64, P = .033).

“In this 80% of patients who have a high-risk soft-tissue sarcoma of the trunk or extremeties, it is worthwhile considering chemotherapy with epirubicin plus ifosfamide, because their prognosis is improved by 20%,” Dr. Gronchi said. “We look forward to further follow-up of this trial to provide confirmation of this interim analysis, as this is the first time that convincing evidence favoring the use of neoadjuvant chemotherapy is provided.”

While the study failed to show any benefit from histologically-tailored regimens, subgroup analysis did suggest that patients with high-grade myxoid liposarcoma who were treated with trabectedin had similar progression-free and overall survival to those treated with epirubicin plus ifosfamide.

“Trabectedin is far less toxic than conventional chemotherapy, so we will now expand this subgroup to assess if there is no difference between the two in terms of outcomes,” Dr. Gronchi said, pointing out that histology-driven therapy was not associated with any detrimental effects.

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®.


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