FOXFIRE-SIRFLOX-FOXFIRE global prospective randomised studies of first-line selective internal radiotherapy (SIRT) in patients with liver metastases from colorectal cancer: KRAS mutation and tumour site analysis

Wasan, Harpreet; Sharma, Ricky A.; Heinemann, Volker; Sharma, Navesh K.; Taı̈eb, Julien; Ricke, Jens; Peeters, Marc; Findlay, Michael; Virdee, P S; Love, Sharon; Moschandreas, Joanna; Dutton, Peter; Gebski, Val; Gray, Alastair; Price, D; Bower, G; Montazeri, A; Gibbs, Peter; Hazel, G. Van

doi:10.1093/annonc/mdx440.018

Cited by 39 publications

(57 citation statements)

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“…Second-line treatment with irinotecan-based regimens has been associated with shorter median progression-free survival [36]. Tumor sidedness is currently undergoing intense study, given the recognition that tumor location is prognostic and predictive [37-39]. Tumor sidedness is not a stratification factor in the EPOCH study because when the study was designed, the importance of this prognostic factor was less understood; however, a preplanned analysis to assess the impact of this factor will be performed.…”

Section: Discussionmentioning

confidence: 99%

TheraSphere Yttrium-90 Glass Microspheres Combined With Chemotherapy Versus Chemotherapy Alone in Second-Line Treatment of Patients With Metastatic Colorectal Carcinoma of the Liver: Protocol for the EPOCH Phase 3 Randomized Clinical Trial

Chauhan¹,

Mulcahy²,

Salem³

et al. 2019

JMIR Res Protoc

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BackgroundColorectal cancer is one of the most common cancers and causes of cancer-related death. Up to approximately 70% of patients with metastatic colorectal cancer (mCRC) have metastases to the liver at initial diagnosis. Second-line systemic treatment in mCRC can prolong survival after development of disease progression during or after first-line treatment and in those who are intolerant to first-line treatment.ObjectiveThe objective of this study is to evaluate the efficacy and safety of transarterial radioembolization (TARE) with TheraSphere yttrium-90 (90Y) glass microspheres combined with second-line therapy in patients with mCRC of the liver who had disease progression during or after first-line chemotherapy.MethodsEPOCH is an open-label, prospective, multicenter, randomized, phase 3 trial being conducted at up to 100 sites in the United States, Canada, Europe, and Asia. Eligible patients have mCRC of the liver and disease progression after first-line chemotherapy with either an oxaliplatin-based or irinotecan-based regimen and are eligible for second-line chemotherapy with the alternate regimen. Patients were randomized 1:1 to the TARE group (chemotherapy with TARE in place of the second chemotherapy infusion and subsequent resumption of chemotherapy) or the control group (chemotherapy alone). The addition of targeted agents is permitted. The primary end points are progression-free survival and hepatic progression-free survival. The study objective will be considered achieved if at least one primary end point is statistically significant. Secondary end points are overall survival, time to symptomatic progression defined as Eastern Cooperative Oncology Group Performance Status score of 2 or higher, objective response rate, disease control rate, quality-of-life assessment by the Functional Assessment of Cancer Therapy-Colorectal Cancer questionnaire, and adverse events. The study is an adaptive trial, comprising a group sequential design with 2 interim analyses with a planned maximum of 420 patients. The study is designed to detect a 2.5-month increase in median progression-free survival, from 6 months in the control group to 8.5 months in the TARE group (hazard ratio [HR] 0.71), and a 3.5-month increase in median hepatic progression-free survival time, from 6.5 months in the control group to 10 months in the TARE group (HR 0.65). On the basis of simulations, the power to detect the target difference in either progression-free survival or hepatic progression-free survival is >90%, and the power to detect the target difference in each end point alone is >80%.ResultsPatient enrollment ended in October 2018. The first interim analysis in June 2018 resulted in continuation of the study without any changes.ConclusionsThe EPOCH study may contribute toward the establishment of the role of combination therapy with TARE and oxaliplatin- or irinotecan-based chemotherapy in the second-line treatment of mCRC of the liver.Trial RegistrationClinicalTrials.gov NCT01483027; https://clinicaltrials.gov/ct2/show/NCT01483027...

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Section: Discussionmentioning

confidence: 99%

TheraSphere Yttrium-90 Glass Microspheres Combined With Chemotherapy Versus Chemotherapy Alone in Second-Line Treatment of Patients With Metastatic Colorectal Carcinoma of the Liver: Protocol for the EPOCH Phase 3 Randomized Clinical Trial

Chauhan¹,

Mulcahy²,

Salem³

et al. 2019

JMIR Res Protoc

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“…Only the results of SIRFLOX study were fully published, and the others were included in abstract presentations. There is a pooled analysis of these three clinical trials in different publications [ 208 , 209 , 210 , 211 , 212 ]. A total of 549 patients were treated with QT alone and 554 were treated with QT plus Yttrium-90, at a median follow-up of 43 months.…”

Section: Hepatic Arterially Directed Therapiesmentioning

confidence: 99%

“…There are results of subgroup analyses of FOXFIRE, SIRFLOX and FOXFIRE-global. There were no OS differences between the treatment arms based on the KRAS mutation status [ 210 ]. OS was significantly greater in the QT plus Yttrium-90 in those with right-sided tumors (22 months vs. 26 months), but not left-sided tumors (24.6 months vs. 26.6 months) [ 211 ].…”

Section: Hepatic Arterially Directed Therapiesmentioning

confidence: 99%

Local Treatments in the Unresectable Patient with Colorectal Cancer Metastasis: A Review from the Point of View of the Medical Oncologist

Torres-Jiménez

Esteban-Villarrubia

Ferreiro-Monteagudo

et al. 2021

Cancers

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For patients with isolated liver metastases from colorectal cancer who are not candidates for potentially curative resections, non-surgical local treatments may be useful. Non-surgical local treatments are classified according to how the treatment is administered. Local treatments are applied directly on hepatic parenchyma, such as radiofrequency, microwave hyperthermia and cryotherapy. Locoregional therapies are delivered through the hepatic artery, such as chemoinfusion, chemoembolization or selective internal radiation with Yttrium 90 radioembolization. The purpose of this review is to describe the different interventional therapies that are available for these patients in routine clinical practice, the most important clinical trials that have tried to demonstrate the effectiveness of each therapy and recommendations from principal medical oncologic societies.

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“…In the SIRFLOX trial, van Hazel et al 63 patients might benefit from TARE. 65 These analyses highlight the necessity for optimized patient selection to maximize the clinical effectiveness of TARE and to provide individualized treatment schemes.…”

Section: Transarterial Radioembolization For Colorectal Liver Metastasesmentioning

confidence: 99%

“…). Analyzing the combined SIRFLOX, FOXFIRE, and FOXFIRE Global clinical trials, Wasan et al65 reported that patients with right-sided CRC showed longer OS if treated with TARE/FOLFOX versus FOLFOX (median OS, 22 months vs. 17.1 months; p = .007). In the same analysis, KRAS status did not affect TARE effectiveness, with no significant OS difference reported for TARE/FOLFOX versus FOLFOX, both in KRAS wild-type and KRAS mutant disease (p .…”

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confidence: 99%

Locoregional Therapies for Colorectal Cancer Liver Metastases: Options Beyond Resection

Uhlig

Lukovic

Dawson

et al. 2021

American Society of Clinical Oncology Educational Book

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Colorectal cancer was the third most common malignancy worldwide in 2018, and most patients present with or develop distant metastases. Colorectal liver metastases are most commonly observed because of the vascular drainage of the colon and superior rectum. Current guidelines recommend surgical resection as first-line treatment; however, 80% to 90% of patients with colorectal liver metastases are ineligible for primary resection. For patients with unresectable disease, a multidisciplinary treatment approach is favored, incorporating systemic therapy and a toolbox of local ablative therapies. These treatments either aim at cytoreduction to enable a conversion to surgical resectability or control of disease progression and spread. Each of these treatments carries unique outcomes and risk profiles, thereby contributing to an individualized treatment strategy for patients with colorectal liver metastases. This review summarizes evidence on hepatic artery infusion, stereotactic body radiation therapy, thermal ablation, transarterial chemoembolization with drug-eluding beads, and transarterial radioembolization for treatment of colorectal liver metastases. Results of large-scale prospective and retrospective studies and international guidelines are discussed to provide detailed background on the current and prospective use of local ablative techniques in management of colorectal liver metastases.

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FOXFIRE-SIRFLOX-FOXFIRE global prospective randomised studies of first-line selective internal radiotherapy (SIRT) in patients with liver metastases from colorectal cancer: KRAS mutation and tumour site analysis

Cited by 39 publications

References 0 publications

TheraSphere Yttrium-90 Glass Microspheres Combined With Chemotherapy Versus Chemotherapy Alone in Second-Line Treatment of Patients With Metastatic Colorectal Carcinoma of the Liver: Protocol for the EPOCH Phase 3 Randomized Clinical Trial

TheraSphere Yttrium-90 Glass Microspheres Combined With Chemotherapy Versus Chemotherapy Alone in Second-Line Treatment of Patients With Metastatic Colorectal Carcinoma of the Liver: Protocol for the EPOCH Phase 3 Randomized Clinical Trial

Local Treatments in the Unresectable Patient with Colorectal Cancer Metastasis: A Review from the Point of View of the Medical Oncologist

Locoregional Therapies for Colorectal Cancer Liver Metastases: Options Beyond Resection

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