Absence of progression, not extent of tumour shrinkage, defines prognosis in soft-tissue sarcoma – An analysis of the EORTC 62012 study of the EORTC STBSG. (September 2016)

• Record Type: Journal Article
• Authors: Grünwald, Viktor; Litière, Saskia; Young, Robin; Messiou, Christina; Lia, Michela; Wardelmann, Eva; van der Graaf, Winette; Gronchi, Alessandro; Judson, Ian
• Is Part Of: European journal of cancer. Volume 64(2016)
• Page Start: 44
• Page End: 51
• Publication Date: 2016-09
• Subjects: Soft-tissue sarcoma -- Chemotherapy -- Tumour shrinkage -- Prognosis; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Cancer; Tumors; Electronic journals; Periodicals; Electronic journals; 616.994
• DOI: 10.1016/j.ejca.2016.05.023
• Languages: English
• ISSNs: 0959-8049

Abstract

Abstract: Background: Anthracycline-based chemotherapy remains the mainstay of first-line treatment in metastatic or advanced soft-tissue sarcoma (STS). Age, performance status, tumour histology and tumour grade are recognised prognostic factors; however, the prognostic value of tumour response and tumour shrinkage is ill-defined. Methods: Patients recruited to the European Organisation for Research and Treatment of Cancer 62012 trial with advanced intermediate or high-grade STS, who received at least one cycle of chemotherapy and one tumour assessment of response, were eligible for this study. Kaplan–Meier estimates of overall survival (OS) by tumour response were computed using a landmark approach after two, four, and six cycles of chemotherapy. The prognostic role of the kinetics of tumour response was analysed by Cox proportional hazards. Results: Three hundred eighty-nine patients were included in this study. Compared to stable or responding patients, patients with progressive disease (PD) after two, four and six cycles of chemotherapy achieved a worse OS: hazard ratio [HR] 2.62 (95% confidence interval [CI] 1.72–4.00), p < 0.001; HR 2.23 (95% CI 1.4–3.56), p = 0.0001; and HR 3.16 (95% CI 1.96–5.08), p = 0.0001, respectively. However, patients with stable or responding disease achieved similar OS outcomes. Correspondingly, patients with an increase in tumour size by 10% or more correlated with a worse OS in Cox proportional hazard analysis. Conclusions: No association between prognosis and amount of tumour shrinkage was detected. Interestingly, an increase in tumour size by at least 10% correlated with a worse OS, but re-defining PD as a ≥10% increase in tumour size did not translate into a better discrimination of survival outcomes for responders versus stable disease. Disease control rather than tumour response is a valuable end-point in advanced or metastatic STS receiving palliative anthracycline-based chemotherapy, supporting the use of time-to-event end-points in future STS trials. Highlights: Extent of remission is not prognostic in advanced or metastatic soft-tissue sarcoma (STS) treated with palliative chemotherapy. Disease control is clinically meaningful in advanced or metastatic STS. Time-to-event end-points are adequate to capture clinical activity in advanced or metastatic STS.