TY - JOUR
T1 - Regorafenib in patients with relapsed advanced or metastatic chordoma
T2 - results of a non-comparative, randomised, double-blind, placebo-controlled, multicentre phase II study
AU - Le Cesne, A.
AU - Chevreau, C.
AU - Perrin, C.
AU - Italiano, A.
AU - Hervieu, A.
AU - Blay, J. Y.
AU - Piperno-Neumann, S.
AU - Saada-Bouzid, E.
AU - Bertucci, F.
AU - Firmin, N.
AU - Kalbacher, E.
AU - Narciso, B.
AU - Schiffler, C.
AU - Yara, S.
AU - Jimenez, M.
AU - Bouvier, C.
AU - Vidal, V.
AU - Chabaud, S.
AU - Duffaud, F.
N1 - Publisher Copyright:
© 2023 The Authors
PY - 2023/6/1
Y1 - 2023/6/1
N2 - Background: REGOBONE multicohort study explored the efficacy and safety of regorafenib for patients with advanced bone sarcomas; this report details the cohort of patients with relapsed advanced or metastatic chordoma. Methods: Patients with relapsed chordoma progressing despite 0-2 prior lines of systemic therapy, were randomised (2: 1) to receive regorafenib (160 mg/day, 21/28 days) or placebo. Patients on placebo could cross over to receive regorafenib after centrally-confirmed progression. The primary endpoint was the progression-free rate at 6 months (PFR-6) (by RECIST 1.1). With one-sided α of 0.05, and 80% power, at least 10/24 progression-free patients at 6 months (PFR-6) were needed for success. Results: From March 2016 to February 2020, 27 patients were enrolled. A total of 23 patients were assessable for efficacy: 7 on placebo, 16 on regorafenib, 16 were men, median age was 66 (32-85) years. At 6 months, in the regorafenib arm, 1 patient was not assessable, 6/14 were non-progressive (PFR-6: 42.9%; one-sided 95% CI = 20.6) 3/14 discontinued regorafenib due to toxicity; and in the placebo arm, 2/5 patients were non-progressive (PFR-6: 40.0%; one-sided 95% CI = 7.6), 2 were non-assessable. Median progression-free survival was 8.2 months (95% CI 4.5-12.9 months) on regorafenib and 10.1 months (95% CI 0.8 months-non evaluable [NE]) on placebo. Median overall survival rates were 28.3 months (95% CI 14.8 months-NE) on regorafenib but not reached in placebo arm. Four placebo patients crossed over to receive regorafenib after centrally-confirmed progression. The most common grade ≥3 regorafenib-related adverse events were hand-foot skin reaction (22%), hypertension (22%), pain (22%), and diarrhoea (17%), with no toxic death. Conclusion: This study failed to show any signal of benefit for regorafenib in patients with advanced/metastatic recurrent chordoma.
AB - Background: REGOBONE multicohort study explored the efficacy and safety of regorafenib for patients with advanced bone sarcomas; this report details the cohort of patients with relapsed advanced or metastatic chordoma. Methods: Patients with relapsed chordoma progressing despite 0-2 prior lines of systemic therapy, were randomised (2: 1) to receive regorafenib (160 mg/day, 21/28 days) or placebo. Patients on placebo could cross over to receive regorafenib after centrally-confirmed progression. The primary endpoint was the progression-free rate at 6 months (PFR-6) (by RECIST 1.1). With one-sided α of 0.05, and 80% power, at least 10/24 progression-free patients at 6 months (PFR-6) were needed for success. Results: From March 2016 to February 2020, 27 patients were enrolled. A total of 23 patients were assessable for efficacy: 7 on placebo, 16 on regorafenib, 16 were men, median age was 66 (32-85) years. At 6 months, in the regorafenib arm, 1 patient was not assessable, 6/14 were non-progressive (PFR-6: 42.9%; one-sided 95% CI = 20.6) 3/14 discontinued regorafenib due to toxicity; and in the placebo arm, 2/5 patients were non-progressive (PFR-6: 40.0%; one-sided 95% CI = 7.6), 2 were non-assessable. Median progression-free survival was 8.2 months (95% CI 4.5-12.9 months) on regorafenib and 10.1 months (95% CI 0.8 months-non evaluable [NE]) on placebo. Median overall survival rates were 28.3 months (95% CI 14.8 months-NE) on regorafenib but not reached in placebo arm. Four placebo patients crossed over to receive regorafenib after centrally-confirmed progression. The most common grade ≥3 regorafenib-related adverse events were hand-foot skin reaction (22%), hypertension (22%), pain (22%), and diarrhoea (17%), with no toxic death. Conclusion: This study failed to show any signal of benefit for regorafenib in patients with advanced/metastatic recurrent chordoma.
KW - recurrent/metastatic chordoma
KW - regorafenib
UR - http://www.scopus.com/inward/record.url?scp=85161356431&partnerID=8YFLogxK
U2 - 10.1016/j.esmoop.2023.101569
DO - 10.1016/j.esmoop.2023.101569
M3 - Article
AN - SCOPUS:85161356431
SN - 2059-7029
VL - 8
JO - ESMO Open
JF - ESMO Open
IS - 3
M1 - 101569
ER -