Eribulin OS Benefit Found For Advanced Liposarcoma, Leiomyosarcoma

Eribulin may offer longer overall survival than dacarbazine for advanced liposarcoma or leiomyosarcoma

medwireNews: The cytotoxic agent eribulin extends the overall survival (OS) of patients with pretreated, advanced liposarcoma or leiomyosarcoma compared with the alkylating agent dacarbazine, phase III study findings suggest.

The open-label, multicentre trial compared 21-day cycles of eribulin (1.4 mg/m2 on days 1 and 8) and dacarbazine (850–1200 mg/m2 on day 1) in patients with intermediate- or high-grade advanced or metastatic disease who had previously received at least two regimens including anthracycline treatment.

OS was a median of 13.5 months for the 228 eribulin-treated patients versus 11.5 months for the 224 dacarbazine-treated patients, giving a significant hazard ratio of 0.77, report Patrick Schöffski, from University Hospital Leuven in Belgium, and co-workers.

The researchers describe the OS gain as “clinically meaningful” in The Lancet, although the benefit did not reach the pre-specified 2.5-month improvement deemed necessary to show “clinical importance.”

The team also notes that the secondary endpoints of progression-free survival and 12-week progression-free survival did not significantly differ between the treatment groups.

None of the patients achieved a complete response to treatment; eribulin and dacarbazine induced a comparable rate of partial response (4 vs 5%), stable disease (52 vs 48%) and objective response (4 vs 5%).

“These data indicate that the secondary endpoints in this study could underestimate the efficacy of eribulin, and therefore might not be an accurate predictor of overall survival benefit in patients with leiomyosarcoma and liposarcoma”, the researchers suggest.

They postulate that the OS-specific benefit of eribulin “might be attributed to the biological effects of eribulin on tumour vascularisation, microenvironment, and metastases” and recommend further tissue sample analysis to determine the relevance of these factors.

Treatment-emergent events that lead to treatment withdrawal occurred in 8% of 226 eribulin-treated patients in the safety population versus 5% of the 224 dacarbazine-treated counterparts, with grade 3 or more severe events in 67% and 56% of participants, respectively.

Dose reduction was required in 26% and 14% of the eribulin and dacarbazine groups, respectively, and dose interruption in 33% and 32%. One death from neutropenic sepsis was considered by the investigators to be possibly linked to eribulin therapy.

Robin Young and Penella Woll, from Weston Park Hospital in Sheffield, UK, discuss when eribulin might best be used in soft-tissue sarcoma in a linked comment.

Noting the low objective response rate, they suggest eribulin “is not attractive as a first-line option” and that patients should be counselled that treatment is to control rather than shrink tumours.

Acknowledging that eribulin has been shown to induce tumour vasculature changes that may make soft-tissue sarcoma more susceptible to follow-up chemotherapy, the commentators agree this may partially explain its OS benefit.

“If eribulin enhances the response to subsequent chemotherapy, should eribulin be used in combination or sequenced with other systemic treatments, and with which other drugs?”, they write.

“Further study of mode of action of eribulin and identification of biomarkers to guide patient selection would help to place it in the algorithm of treatments for relapse.”

References

Schöffski P, Chawla S, Maki RG, et al. Eribulin versus dacarbazine in previously treated patients with advanced liposarcoma or leiomyosarcoma: a randomised, open-label, multicentre, phase 3 trial. Lancet 2016; Advance online publication 10 February. DOI: http://dx.doi.org/10.1016/S0140-6736(15)01283-0

Young RJ, Woll PJ. Eribulin in soft-tissue sarcoma. Lancet 2016; Advance online publication 10 February. DOI: http://dx.doi.org/10.1016/S0140-6736(16)00162-8

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