Multi institutional phase II trial of single agent regorafenib in refractory advanced biliary cancers.

Kim, Richard D.; Poklepovic, Andrew; Nixon, Andrew B.; Kim, Dae Won; Soares, Heloisa P.; Kim, Jongphil; Zhou, Jun; Tariq, Fatima; Burgess, Natalie; Sanoff, Hanna K.

doi:10.1200/jco.2018.36.15_suppl.4082

Cited by 9 publications

(10 citation statements)

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“…Sun et al 19 reported a median PFS of 15.6 weeks in 43 patients receiving regorafenib monotherapy. In the phase II trial from Kim et al, 20 median PFS was 2.8 months (39 patients). In both of these trials and the one reported here, the IH tumor location was predominant (70% in REACHIN, 62% Sun et al, 19 69% Kim et al 20 ).…”

Section: Discussionmentioning

confidence: 98%

Regorafenib after failure of gemcitabine and platinum-based chemotherapy for locally advanced/metastatic biliary tumors: REACHIN, a randomized, double-blind, phase II trial

et al. 2020

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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 ¼ 42), perihilar (n ¼ 6), or extrahepatic (n ¼ 9) cholangiocarcinoma, or gallbladder carcinoma (n ¼ 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): 6.0e15.9] in the regorafenib group and 6.3 weeks (95% CI: 3.9e7.0) in the placebo group (P ¼ 0.002). Fourteen of 33 patients (42%) in the regorafenib group had a dose reduction. Stable disease rates were 74% (95% CI: 59e90) in the regorafenib group and 34% with placebo (95% CI: 18e51; P ¼ 0.002). Median PFS in the regorafenib group was 3.0 months (95% CI: 2.3e4.9) and 1.5 months (95% CI: 1.2e2.0) in the placebo group (hazard ratio 0.49; 95% CI: 0.29e0.81; P ¼ 0.004) and median overall survival was 5.3 months (95% CI: 2.7e10.5) and 5.1 months (95% CI: 3.0e6.4), respectively (P ¼ 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. Clinical Trial Registration: The trial is registered in the European Clinical Trials Register database (EudraCT 2012-005626-30) and at ClinicalTrials.gov (NCT02162914).

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Section: Discussionmentioning

confidence: 98%

Regorafenib after failure of gemcitabine and platinum-based chemotherapy for locally advanced/metastatic biliary tumors: REACHIN, a randomized, double-blind, phase II trial

et al. 2020

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“…Regorafenib has shown survival benefit in patients with chemotherapyrefractory advanced and metastatic biliary adenocarcinoma in two singlearm, open-label, phase 2 studies [77,78]. In the multi-institutional study (NCT02115542) with 32 patients evaluable for efficacy, the 6-, 12-, and 18month OS rates were 51%, 35%, and 35%, respectively [77]. Based on the primary endpoint (6-month OS), regorafenib was deemed to have good activity if 43.8% of evaluable patients survived ≥ 6 months (α = 0.10, 86% power).…”

Section: Biliary Tract Cancermentioning

confidence: 99%

“…To date, no new safety concerns have arisen from studies in other cancer types, including gastric cancer [57], STS/bone sarcoma [65,68,69,72], biliary tract cancer [77,78,80], or glioblastoma [86], with the nature, incidence, and severity of AEs (including skin toxicities) consistent with those described in the label [1,2]. In INTEGRATE, there was a lower incidence of grade 3/4 HFSR and fatigue versus CORRECT, possibly due to racial differences affecting drug absorption/pharmacokinetics or improved management of regorafenib-related toxicities [57].…”

Section: Safety Of Regorafenib Across Tumor Typesmentioning

confidence: 99%

Evolving role of regorafenib for the treatment of advanced cancers

Grothey

Blay

Pavlakis

et al. 2020

Cancer Treatment Reviews

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Regorafenib is an oral tyrosine kinase inhibitor (TKI) approved for the treatment of refractory metastatic colorectal cancer (mCRC), advanced gastrointestinal stromal tumors (GIST) previously treated with imatinib and sunitinib, and unresectable hepatocellular carcinoma (HCC) following progression on sorafenib. Regorafenib was initially approved for mCRC based on improved overall survival (OS) in the randomized, placebo-controlled, phase 3 CORRECT trial, which was confirmed in an expanded population of Asian patients in the randomized, placebo-controlled phase 3 CONCUR trial. Approvals in GIST, and more recently in HCC, were based on the results from the randomized, placebocontrolled, phase 3 GRID and RESORCE trials, respectively. In this review, we provide a comprehensive summary of the clinical evidence for approval of regorafenib in mCRC, GIST, and HCC, present emerging evidence of regorafenib activity in other tumor types (namely, gastroesophageal cancer, sarcomas, biliary tract cancer, and glioblastoma), and discuss trials in progress within the context of regorafenib's mechanism of action. We describe recent advances and key lessons learned with regorafenib, including the importance of managing common drug-related toxicities using doseoptimization strategies, the search for biomarkers to predict response to treatment, and highlight some of the unaddressed questions and future directions for regorafenib across tumors.

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“…The most common adverse events were hypophosphatemia, hand-foot skin reaction, hypertension and increased serum bilirubin. In another phase II trial regorafenib was studied in 39 CCA patients which have failed one prior gemcitabine-based systemic therapy (92). Median PFS was 3.7 months and median OS 9.9 months, with PR achieved in 2 patients (6.2%) and SD in 18 subjects (56.2%).…”

Section: Angiogenesis Inhibitorsmentioning

confidence: 99%

Second-line Treatment in Advanced Biliary Tract Cancer: Today and Tomorrow

et al. 2020

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Biliary tract cancer (BTC) patients usually have poor prognosis. Whereas combination chemotherapy has been shown to improve survival in the frontline setting, second-line treatment is subject to a lot of debate in the scientific community. Recent data of the ABC-06 trial has provided slight evidence for the use of second-line chemotherapy after progression on cisplatin plus gemcitabine combination. In this study, mFOLFOX plus active symptom control (ASC) improved overall survival (OS) after progression on cisplatingemcitabine combination compared with ASC alone, with an increase in 6-and 12-month OS rate. Although genomic studies have paved the way for a new age in cancer management, the "Precision Medicine Era" in BTC is still limited to intrahepatic cholangiocarcinoma and primarily focused on isocitrate dehydrogenase (IDH) and fibroblast growth factor receptor (FGFR) targeted therapies. We herein review recent published data regarding the use of second-line treatment after failure of standard first-line therapies in BTC patients, with a particular focus on ongoing active and recruiting clinical trials.

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Multi institutional phase II trial of single agent regorafenib in refractory advanced biliary cancers.

Cited by 9 publications

References 0 publications

Regorafenib after failure of gemcitabine and platinum-based chemotherapy for locally advanced/metastatic biliary tumors: REACHIN, a randomized, double-blind, phase II trial

Regorafenib after failure of gemcitabine and platinum-based chemotherapy for locally advanced/metastatic biliary tumors: REACHIN, a randomized, double-blind, phase II trial

Evolving role of regorafenib for the treatment of advanced cancers

Second-line Treatment in Advanced Biliary Tract Cancer: Today and Tomorrow

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