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ORIGINAL ARTICLES: SARCOMA

Predictive and prognostic factors associated with soft tissue sarcoma response to chemotherapy: a subgroup analysis of the European Organisation for Research and Treatment of Cancer 62012 study

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Pages 1013-1020 | Received 06 Feb 2017, Accepted 29 Mar 2017, Published online: 21 Apr 2017
 

Abstract

Background: The European Organization for Research and Treatment of Cancer (EORTC) 62012 study was a Phase III trial of doxorubicin versus doxorubicin–ifosfamide chemotherapy in 455 patients with advanced soft tissue sarcoma (STS). Analysis of the main study showed that combination chemotherapy improved tumor response and progression-free survival, but differences in overall survival (OS) were not statistically significant. We analyzed factors prognostic for tumor response and OS, and assessed histological subgroup and tumor grade as predictive factors to identify patients more likely to benefit from combination chemotherapy.

Methods: Central pathology review was performed by six reference pathologists. Gender, age, performance status, time from first presentation with sarcoma to starting palliative chemotherapy, tumor grade, histological subgroup, primary tumor site involvement, and sites of metastases were assessed as prognostic factors.

Results: Three hundred and ten patients were included in this study. Discordance between local and central pathology opinion of tumor histology and tumor grade was observed in 98 (32%) and 122 (39%) cases, respectively. In multivariate analysis, liposarcoma patients had improved tumor response compared to other histological subgroups, whilst patients with metastases other than lung, liver or bone had a poorer response [odds ratio (OR) 0.42, 95% confidence interval (CI) 0.23–0.78; p = 0.006]. Patients with bone metastases had reduced OS [hazard ratio (HR) 1.56, 95% CI 1.16–2.09; p = 0.003]. By central pathology review, patients with undifferentiated pleomorphic sarcoma (UPS) had improved tumor response and OS with doxorubicin–ifosfamide compared to single-agent doxorubicin (OR 9.90, 95% CI 1.93–50.7 and HR 0.44, 95% CI 0.26–0.79, respectively). Grade III tumors had improved response with combination chemotherapy but there was no interaction between chemotherapy and grade on OS.

Conclusions: Prospective central pathology review of tumor histology should be integrated into future STS clinical trials. Doxorubicin–ifosfamide may be most appropriate for young, fit patients with poorly differentiated Grade III tumors including UPS.

Acknowledgments

The authors would like to thank all the patients and physicians who participated in the EORTC 62012 trial.

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

Additional information

Funding

M.L. received a fellowship supported by Fonds Cancer (FOCA; Brussels, Belgium). This study was conducted by the EORTC.

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