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Clinical Trial
. 2023 Dec;129(12):1940-1948.
doi: 10.1038/s41416-023-02413-9. Epub 2023 Nov 1.

Regorafenib in patients with advanced Ewing sarcoma: results of a non-comparative, randomised, double-blind, placebo-controlled, multicentre Phase II study

Florence Duffaud  1 , Jean-Yves Blay  2 , Axel Le Cesne  3 , Christine Chevreau  4 , Pascaline Boudou-Rouquette  5 , Elsa Kalbacher  6 , Nicolas Penel  7 , Christophe Perrin  8 , Valérie Laurence  9 , Emmanuelle Bompas  10 , Esma Saada-Bouzid  11 , Corinne Delcambre  12 , François Bertucci  13 , Mathilde Cancel  14 , Camille Schiffler  15 , Laure Monard  16 , Corinne Bouvier  17 , Vincent Vidal  18 , Nathalie Gaspar  19 , Sylvie Chabaud  15
Affiliations
Clinical Trial

Regorafenib in patients with advanced Ewing sarcoma: results of a non-comparative, randomised, double-blind, placebo-controlled, multicentre Phase II study

Florence Duffaud et al. Br J Cancer. 2023 Dec.

Abstract

Background: The REGOBONE multi-cohort study explored the efficacy and safety of regorafenib for patients with advanced bone sarcomas; this report details the Ewing sarcoma (ES) cohort.

Methods: Patients with relapsed ES progressing despite prior standard therapy, were randomised (2:1) to receive regorafenib or placebo. Patients on placebo could crossover to receive regorafenib after centrally confirmed progression. The primary endpoint was the progression-free rate at 8 weeks. With one-sided α of 0.05, and 80% power, at least 14/24 progression-free patients at 8 weeks were needed for success.

Results: From September 2014 to November 2019, 41 patients were accrued. 36 patients were evaluable for efficacy: 23 on regorafenib and 13 on placebo. Thirteen patients (56%; one-sided 95% CI [37.5%-[)) were progression-free at 8 weeks on regorafenib vs. 1 (7.7%; 95% CI [0.4%-[) on placebo. Median PFS was 11.4 weeks on regorafenib, and 3.9 weeks on placebo. Ten placebo patients crossed over to receive regorafenib after progression. The most common grade ≥3 regorafenib-related adverse events were pain (22%), asthenia (17%), thrombocytopenia (13%) and diarrhoea (13%).

Conclusion: Although the primary endpoint was not met statistically in this randomised cohort, there is evidence to suggest that regorafenib might modestly delay tumour progression in relapsed ES after failure of prior chemotherapy.

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Conflict of interest statement

FD received travel grants from Pharmamar, and Leo Pharma, attended advisory boards for Bayer, Lilly. CC attended advisory boards for Leo Pharma, JYB receives research support and honoraria from Eisei, Eli Lilly, MSD, BMS, GSK, Ignyta, Novartis, Pharmamar and Roche unrelated to this work. AL, AI, PB, EK, NP, CP, VL, EB, ESBB, FB, CS, VL, MC, CS,LM, VV, NG and SC declare no competing interests.

Figures

Fig. 1
Fig. 1
Trial profile—study population—consort diagram.
Fig. 2
Fig. 2
Progression-free survival curves per blinded central review.
Fig. 3
Fig. 3
Overall survival curves, including crossed over of 77% of placebo patients who received open-label regorafenib.
Fig. 4
Fig. 4
Swimmer plots showing initial PFS and PFS after crossover for the ten patients initially randomised to placebo who subsequently received open-label regorafenib.
Fig. 5
Fig. 5
Waterfall plots on regorafenib arm and placebo arm, in supplementary materials.
See this image and copyright information in PMC

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