Advancing the treatment of sarcoma

Neoadjuvant chemotherapy with three full-dose courses of the anthracycline epirubicin plus ifosfamide has a substantial clinical benefit over ‘histology-adapted’ chemotherapies in patients with localised high-risk soft tissue sarcomas (STS).

Neoadjuvant chemotherapy with three full-dose courses of the anthracycline epirubicin plus ifosfamide has a substantial clinical benefit over ‘histology-adapted’ chemotherapies in patients with localised high-risk soft tissue sarcomas (STS). These were the findings of a prospective randomised study (third futility analysis) reviewed in a Late-Breaking Abstract presentation yesterday by Dr Alessandro Gronchi from Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy (Abstract LBA6_PR). In 286 adult STS patients at high risk of relapse, the probability of relapse-free survival (RFS; primary endpoint) at 46 months (median follow-up 12.34 months) was 62% with epirubicin plus ifosfamide versus 38% with histology-driven treatment (p=0.004).

Dr Gronchi noted similar overall survival (OS) data (89% versus 64%; p=0.033), resulting in an increase of >20% in RFS and ≥10% in OS with the anthracycline-containing regimen compared with other chemotherapy regimens.

Subgroup analysis by histologically-tailored regimen suggested that patients with high-grade myxoid liposarcoma derived similar progression-free survival (PFS) and OS benefits from trabectedin compared with epirubicin plus ifosfamide. This patient subgroup will be expanded to further investigate this effect.

Further sarcoma data were reviewed during a Proffered Paper Session on Saturday in two presentations. In the first, trabectedin doubled median PFS (primary endpoint) compared with best supportive care (BSC) in a phase III study of 103 patients with pre-treated advanced STS (3.1 months versus 1.5 months, respectively; hazard ratio [HR] 0.39; 95% confidence interval [CI] 0.24–0.64; p<0.0001). Dr Axel Le Cesne from Institut de Cancérologie Gustave Roussy, Villejuif, France noted that trabectedin had greatest PFS benefit compared with BSC in patients with lipo-leiomyosarcoma (5.1 months versus 1.4 months, respectively; HR 0.29; 95% CI 0.15–0.55; p<0.0001; Abstract 1396O). A similar degree of benefit has been reported with trabectedin in recent trials with similar patient populations.

In the second presentation, analyses of almost 27,000 sarcoma and connective tissue tumour patients from a French database (NETSARC) revealed a significantly lower rate of local relapse in patients who had been presented to a NETSARC multidisciplinary tumour board (NMTB) prior to initial treatment compared with those who had not (p<0.0001 at a median follow-up of 26 months; Abstract 1397O). Reviewing the data, Professor Jean-Yves Blay from Université Claude Bernard, Lyon, France, noted that a lack of presentation to an NMTB was also an independent unfavourable prognostic factor for relapse on multivariate analysis (HR 1.8; p<0.0001), along with patient age and tumour grade, size and location. These observations provide a strong rationale for multidisciplinary discussion prior to initial treatment of patients with sarcoma. Professor Blay pointed out that a longer follow-up period is needed to evaluate the impact of NMTB presentation on metastasis-free and overall survival.

This article appeared in the Tuesday edition of the Daily Reporter