Regorafenib PFS Improvement Reported For Non-Adipocytic Soft Tissue Sarcoma

Regorafenib trial indicates progression-free survival gain for patients with leiomyosarcoma and synovial sarcoma but not liposarcoma who have previously received anthracycline-based chemotherapy

medwireNews: Phase II results published in The Lancet Oncology indicate that patients with advanced non-adipocytic soft tissue sarcoma who are resistant or intolerant to doxorubicin or other anthracycline-based regimens may benefit from treatment with the multikinase inhibitor regorafenib .

The primary endpoint of median progression-free survival (PFS) was significantly longer with regorafenib 160 mg/day for 3 weeks of a 4-week cycle compared with placebo in three out of four of the REGOSARC patient cohorts of differing sarcoma types, report Nicolas Penel, from Centre Oscar Lambret, Lille, France, and co-workers.

This was true for the 56 patients with leiomyosarcoma (median 3.7 vs 1.8 months, hazard ratio [HR]=0.46), the 27 patients with synovial sarcoma (5.6 vs 1.0 months, HR=0.10) and the 55 patients with other types of sarcoma, mainly undifferentiated pleomorphic sarcomas, malignant solitary fibrous tumours, angiosarcomas and fibrosarcomas (2.9 vs 1.0, HR=0.46).

By contrast, median PFS was comparable in the regorafenib and placebo treatment arms for the 43 patients with liposarcoma, at 1.1 versus 1.7 months and an HR of 0.89.

“Until we know more about mechanisms of resistance, we do not recommend any further trials assessing the activity of regorafenib in unselected patients with liposarcoma”, the researchers comment.

The secondary endpoint of overall survival was affected by the crossover trial design and was longer in patients given regorafenib than placebo for patients with leiomyosarcoma (HR=0.50), synovial sarcoma (HR=0.87) and other types of sarcoma (HR=0.75) but did not reach statistical significance.

But the author of an accompanying comment, John Healey, from Memorial Sloan Kettering Cancer Center in New York, USA, emphasizes that the doubling of median overall survival for the patients with leiomyosarcoma (21.0 vs 9.1 months) and synovial sarcoma (13.4 vs 6.7 months) “has great clinical significance”.

“Despite the absence of statistical significance, this strongly supports further investigation for the use of regorafenib in leiomyosarcoma and synovial sarcoma, and possibly in other non-adipocytic histological subtypes”, he writes, adding that the “wide heterogeneity in histology and behaviour” may explain the lack of efficacy in the liposarcoma group.

Noting that the REGOSARC trial will in the future describe PFS in patients who had and had not previously been treated with pazopanib, the commentator says that further research must now compare competing agents for each histological soft tissue sarcoma.

Nevertheless, John Healey concludes that surgery plays a key role in sarcoma management: “If resectable with an R0 margin, even metastatic sarcoma can be cured with more durable complete responses than any existing systemic agents.

“Thus the collaborative nature of multimodality therapy for sarcomas should be remembered and supported as follow-up studies of regorafenib and other agents are planned.” 


Mir O, Brodowicz T, Italiano A, et al. Safety and efficacy of regorafenib in patients with advanced soft tissue sarcoma (REGOSARC): a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Oncol; Advance online publication 14 October 2016. DOI:

Healey JH. Regorafenib: efficacy in multiple refractory sarcoma types. Lancet Oncol; Advance online publication 14 October 2016. DOI:

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