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Title
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Regorafenib after failure of gemcitabine and platinum-based chemotherapy for locally advanced/metastatic biliary tumors: REACHIN, a randomized, double-blind, phase II trial
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Author
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Abstract
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| Background: There is a high unmet clinical need for treatments of advanced/metastatic biliary tract cancers after progression on first-line chemotherapy. Regorafenib has demonstrated efficacy in some gastrointestinal tumors that progress on standard therapies. Patients and methods: REACHIN was a multicenter, double-blind, placebo-controlled, randomized phase II study designed to evaluate the safety and efficacy of regorafenib in patients with nonresectable/metastatic biliary tract cancer that progressed after gemcitabine/platinum chemotherapy. Patients were randomly assigned 1 : 1 to best supportive care plus either regorafenib 160 mg once daily 3 weeks on/1 week off or placebo until progression or unacceptable toxicity. No crossover was allowed. The primary objective was progression-free survival (PFS). Secondary objectives were response rate, overall survival, and translational analysis. Results: Sixty-six patients with intrahepatic (n = 42), perihilar (n = 6), or extrahepatic (n = 9) cholangiocarcinoma, or gallbladder carcinoma (n = 9) were randomized, 33 to each treatment group (33 per group). At a median follow-up of 24 months, all patients had progressed and six patients were alive. Median treatment duration was 11.0 weeks [95% confidence interval (CI): 6.0-15.9] in the regorafenib group and 6.3 weeks (95% CI: 3.9-7.0) in the placebo group (P = 0.002). Fourteen of 33 patients (42%) in the regorafenib group had a dose reduction. Stable disease rates were 74% (95% CI: 59-90) in the regorafenib group and 34% with placebo (95% CI: 18-51; P = 0.002). Median PFS in the regorafenib group was 3.0 months (95% CI: 2.3-4.9) and 1.5 months (95% CI: 1.2-2.0) in the placebo group (hazard ratio 0.49; 95% CI: 0.29-0.81; P = 0.004) and median overall survival was 5.3 months (95% CI: 2.7-10.5) and 5.1 months (95% CI: 3.0-6.4), respectively (P = 0.28). There were no unexpected/new safety signals. Conclusion: Regorafenib significantly improved PFS and tumor control in patients with previously treated metastatic/unresectable biliary tract cancer in the second- or third-line setting. |
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Language
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English
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Source (journal)
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Annals of oncology / European Society for Medical Oncology. - Amsterdam
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Publication
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Amsterdam
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2020
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ISSN
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0923-7534
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DOI
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10.1016/J.ANNONC.2020.05.018
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Volume/pages
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31
:9
(2020)
, p. 1169-1177
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ISI
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000562396600012
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Pubmed ID
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32464280
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Full text (Publisher's DOI)
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Full text (publisher's version - intranet only)
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