Randomized Double-Blind Phase II Study of Regorafenib in Patients With Metastatic Osteosarcoma

Lara Davis, Vanessa Bolejack, Christopher Ryan, Kristen N. Ganjoo, Elizabeth T. Loggers, Sant Chawla, Mark Agulnik, Michael B. Livingston, Damon Reed, Vicky Keedy, Daniel Rushing, Scott Okuno, Denise K. Reinke, Richard F. Riedel, Steven Attia, Leo Mascarenhas, Robert G. Maki

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

PURPOSE: SARC024 is a phase II clinical trial of the multikinase inhibitor regorafenib in specific sarcoma subtypes, including advanced osteosarcoma. We hypothesized that regorafenib would improve progression-free survival (PFS) in patients with sarcoma and report the results of the osteosarcoma cohort. PATIENTS AND METHODS: This trial enrolled patients with progressive metastatic osteosarcoma with measurable disease by RECIST who had received at least one prior line of therapy. Patients were randomly assigned at a ratio of one to one to regorafenib or placebo. Crossover was allowed at time of disease progression. PFS was the primary end point of the study, which was powered to detect a difference of at least 3 months in median PFS. RESULTS: Forty-two patients from 12 centers were enrolled between September 2014 and May 2018. Median age was 37 years (range, 18 to 76 years). Patients had received an average of 2.3 prior therapy regimens. Ten patients receiving placebo crossed over to active drug at time of progression. Study enrollment was stopped early, after a data safety monitoring committee review. Median PFS was significantly improved with regorafenib versus placebo: 3.6 months (95% CI, 2.0 to 7.6 months) versus 1.7 months (95% CI, 1.2 to 1.8 months), respectively (hazard ratio, 0.42; 95% CI, 0.21 to 0.85; P = .017). In the context of the crossover design, there was no statistically significant difference in overall survival. Fourteen (64%) of 22 patients initially randomly assigned to regorafenib experienced grade 3 to 4 events attributed to treatment, including one grade 4 colonic perforation. CONCLUSION: The study met its primary end point, demonstrating activity of regorafenib in patients with progressive metastatic osteosarcoma. No new safety signals were observed. Regorafenib should be considered a treatment option for patients with relapsed metastatic osteosarcoma.

Original languageEnglish (US)
Pages (from-to)1424-1431
Number of pages8
JournalJournal of clinical oncology : official journal of the American Society of Clinical Oncology
Volume37
Issue number16
DOIs
StatePublished - Jun 1 2019

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Osteosarcoma
Disease-Free Survival
Placebos
Sarcoma
Clinical Trials Data Monitoring Committees
Safety
regorafenib
Phase II Clinical Trials
Therapeutics
Cross-Over Studies
Disease Progression
Survival

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Randomized Double-Blind Phase II Study of Regorafenib in Patients With Metastatic Osteosarcoma. / Davis, Lara; Bolejack, Vanessa; Ryan, Christopher; Ganjoo, Kristen N.; Loggers, Elizabeth T.; Chawla, Sant; Agulnik, Mark; Livingston, Michael B.; Reed, Damon; Keedy, Vicky; Rushing, Daniel; Okuno, Scott; Reinke, Denise K.; Riedel, Richard F.; Attia, Steven; Mascarenhas, Leo; Maki, Robert G.

In: Journal of clinical oncology : official journal of the American Society of Clinical Oncology, Vol. 37, No. 16, 01.06.2019, p. 1424-1431.

Research output: Contribution to journalArticle

Davis, L, Bolejack, V, Ryan, C, Ganjoo, KN, Loggers, ET, Chawla, S, Agulnik, M, Livingston, MB, Reed, D, Keedy, V, Rushing, D, Okuno, S, Reinke, DK, Riedel, RF, Attia, S, Mascarenhas, L & Maki, RG 2019, 'Randomized Double-Blind Phase II Study of Regorafenib in Patients With Metastatic Osteosarcoma', Journal of clinical oncology : official journal of the American Society of Clinical Oncology, vol. 37, no. 16, pp. 1424-1431. https://doi.org/10.1200/JCO.18.02374
Davis, Lara ; Bolejack, Vanessa ; Ryan, Christopher ; Ganjoo, Kristen N. ; Loggers, Elizabeth T. ; Chawla, Sant ; Agulnik, Mark ; Livingston, Michael B. ; Reed, Damon ; Keedy, Vicky ; Rushing, Daniel ; Okuno, Scott ; Reinke, Denise K. ; Riedel, Richard F. ; Attia, Steven ; Mascarenhas, Leo ; Maki, Robert G. / Randomized Double-Blind Phase II Study of Regorafenib in Patients With Metastatic Osteosarcoma. In: Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2019 ; Vol. 37, No. 16. pp. 1424-1431.
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abstract = "PURPOSE: SARC024 is a phase II clinical trial of the multikinase inhibitor regorafenib in specific sarcoma subtypes, including advanced osteosarcoma. We hypothesized that regorafenib would improve progression-free survival (PFS) in patients with sarcoma and report the results of the osteosarcoma cohort. PATIENTS AND METHODS: This trial enrolled patients with progressive metastatic osteosarcoma with measurable disease by RECIST who had received at least one prior line of therapy. Patients were randomly assigned at a ratio of one to one to regorafenib or placebo. Crossover was allowed at time of disease progression. PFS was the primary end point of the study, which was powered to detect a difference of at least 3 months in median PFS. RESULTS: Forty-two patients from 12 centers were enrolled between September 2014 and May 2018. Median age was 37 years (range, 18 to 76 years). Patients had received an average of 2.3 prior therapy regimens. Ten patients receiving placebo crossed over to active drug at time of progression. Study enrollment was stopped early, after a data safety monitoring committee review. Median PFS was significantly improved with regorafenib versus placebo: 3.6 months (95{\%} CI, 2.0 to 7.6 months) versus 1.7 months (95{\%} CI, 1.2 to 1.8 months), respectively (hazard ratio, 0.42; 95{\%} CI, 0.21 to 0.85; P = .017). In the context of the crossover design, there was no statistically significant difference in overall survival. Fourteen (64{\%}) of 22 patients initially randomly assigned to regorafenib experienced grade 3 to 4 events attributed to treatment, including one grade 4 colonic perforation. CONCLUSION: The study met its primary end point, demonstrating activity of regorafenib in patients with progressive metastatic osteosarcoma. No new safety signals were observed. Regorafenib should be considered a treatment option for patients with relapsed metastatic osteosarcoma.",
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AU - Davis, Lara

AU - Bolejack, Vanessa

AU - Ryan, Christopher

AU - Ganjoo, Kristen N.

AU - Loggers, Elizabeth T.

AU - Chawla, Sant

AU - Agulnik, Mark

AU - Livingston, Michael B.

AU - Reed, Damon

AU - Keedy, Vicky

AU - Rushing, Daniel

AU - Okuno, Scott

AU - Reinke, Denise K.

AU - Riedel, Richard F.

AU - Attia, Steven

AU - Mascarenhas, Leo

AU - Maki, Robert G.

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N2 - PURPOSE: SARC024 is a phase II clinical trial of the multikinase inhibitor regorafenib in specific sarcoma subtypes, including advanced osteosarcoma. We hypothesized that regorafenib would improve progression-free survival (PFS) in patients with sarcoma and report the results of the osteosarcoma cohort. PATIENTS AND METHODS: This trial enrolled patients with progressive metastatic osteosarcoma with measurable disease by RECIST who had received at least one prior line of therapy. Patients were randomly assigned at a ratio of one to one to regorafenib or placebo. Crossover was allowed at time of disease progression. PFS was the primary end point of the study, which was powered to detect a difference of at least 3 months in median PFS. RESULTS: Forty-two patients from 12 centers were enrolled between September 2014 and May 2018. Median age was 37 years (range, 18 to 76 years). Patients had received an average of 2.3 prior therapy regimens. Ten patients receiving placebo crossed over to active drug at time of progression. Study enrollment was stopped early, after a data safety monitoring committee review. Median PFS was significantly improved with regorafenib versus placebo: 3.6 months (95% CI, 2.0 to 7.6 months) versus 1.7 months (95% CI, 1.2 to 1.8 months), respectively (hazard ratio, 0.42; 95% CI, 0.21 to 0.85; P = .017). In the context of the crossover design, there was no statistically significant difference in overall survival. Fourteen (64%) of 22 patients initially randomly assigned to regorafenib experienced grade 3 to 4 events attributed to treatment, including one grade 4 colonic perforation. CONCLUSION: The study met its primary end point, demonstrating activity of regorafenib in patients with progressive metastatic osteosarcoma. No new safety signals were observed. Regorafenib should be considered a treatment option for patients with relapsed metastatic osteosarcoma.

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