Second‐line treatment of hepatocellular carcinoma after sorafenib: Characterizing treatments used over the past 10 years and real‐world eligibility for cabozantinib, regorafenib, and ramucirumab

Abstract Background The CELESTIAL, RESORCE, and REACH‐2 trials showed survival benefit of cabozantinib, regorafenib, and ramucirumab, respectively, in hepatocellular carcinoma (HCC) patients treated with sorafenib who had good performance status (ECOG 0‐1) and liver function (Child‐Pugh‐A). This stu...

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Main Authors: Andrea S. Fung, Vincent C. Tam, Daniel E. Meyers, Hao‐Wen Sim, Jennifer J. Knox, Valeriya Zaborska, Janine Davies, Yoo‐Joung Ko, Eugene Batuyong, Haider Samawi, Winson Y. Cheung, Richard Lee‐Ying
Format: Article
Language:English
Published: Wiley 2020-07-01
Series:Cancer Medicine
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Online Access:https://doi.org/10.1002/cam4.3116
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author Andrea S. Fung
Vincent C. Tam
Daniel E. Meyers
Hao‐Wen Sim
Jennifer J. Knox
Valeriya Zaborska
Janine Davies
Yoo‐Joung Ko
Eugene Batuyong
Haider Samawi
Winson Y. Cheung
Richard Lee‐Ying
author_facet Andrea S. Fung
Vincent C. Tam
Daniel E. Meyers
Hao‐Wen Sim
Jennifer J. Knox
Valeriya Zaborska
Janine Davies
Yoo‐Joung Ko
Eugene Batuyong
Haider Samawi
Winson Y. Cheung
Richard Lee‐Ying
author_sort Andrea S. Fung
collection DOAJ
description Abstract Background The CELESTIAL, RESORCE, and REACH‐2 trials showed survival benefit of cabozantinib, regorafenib, and ramucirumab, respectively, in hepatocellular carcinoma (HCC) patients treated with sorafenib who had good performance status (ECOG 0‐1) and liver function (Child‐Pugh‐A). This study characterizes subsequent treatments received by HCC patients after sorafenib, and determines the proportion of patients eligible for novel therapies if strict eligibility criteria (SEC) were utilized compared to more liberal modified eligibility criteria (MEC, including ECOG 2, Child‐Pugh‐B7). Methods HCC patients who received sorafenib between 2008 and 2017 were included from the Canadian HCC CHORD Database. Patients were classified as eligible or ineligible based on available CELESTIAL, RESORCE, and REACH‐2 trial SEC or MEC. Median overall survival (mOS) was assessed using the Kaplan‐Meier method. Results A total of 730 patients were identified; and 172 (23.6%) received subsequent treatment. Patients who received subsequent treatment had longer mOS than those who did not (12.1 vs 3.3 months; P < .001). Using SEC, only 13.1% of patients would be eligible for cabozantinib, regorafenib, or ramucirumab. Expanding eligibility to include patients who meet MEC increased the proportion of eligible patients to 31.7%. Higher ineligibility for regorafenib and ramucirumab was driven by trial‐specific criteria, including sorafenib intolerance (28%) for RESORCE and AFP <400 (58.9%) for REACH‐2. Conclusions A small proportion of real‐world HCC patients would be eligible for cabozantinib, regorafenib, or ramucirumab if SEC in clinical trials were followed, while more than double would be eligible if MEC were applied. Patients who received subsequent treatment had improved mOS, regardless of whether they met SEC or MEC.
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spelling doaj-art-f4695cfcaa624e019d0cbdbba425df4f2025-08-20T01:58:43ZengWileyCancer Medicine2045-76342020-07-019134640464710.1002/cam4.3116Second‐line treatment of hepatocellular carcinoma after sorafenib: Characterizing treatments used over the past 10 years and real‐world eligibility for cabozantinib, regorafenib, and ramucirumabAndrea S. Fung0Vincent C. Tam1Daniel E. Meyers2Hao‐Wen Sim3Jennifer J. Knox4Valeriya Zaborska5Janine Davies6Yoo‐Joung Ko7Eugene Batuyong8Haider Samawi9Winson Y. Cheung10Richard Lee‐Ying11Tom Baker Cancer Centre Calgary AB CanadaTom Baker Cancer Centre Calgary AB CanadaTom Baker Cancer Centre Calgary AB CanadaNHMRC Clinical Trials Centre University of Sydney Camperdown NSW AustraliaPrincess Margaret Cancer Centre Toronto ON CanadaBC Cancer Agency Vancouver Centre Vancouver BC CanadaBC Cancer Agency Vancouver Centre Vancouver BC CanadaSunnybrook Health Sciences Centre – Odette Cancer Centre Toronto ON CanadaTom Baker Cancer Centre Calgary AB CanadaSt. Michael's Hospital Toronto ON CanadaTom Baker Cancer Centre Calgary AB CanadaTom Baker Cancer Centre Calgary AB CanadaAbstract Background The CELESTIAL, RESORCE, and REACH‐2 trials showed survival benefit of cabozantinib, regorafenib, and ramucirumab, respectively, in hepatocellular carcinoma (HCC) patients treated with sorafenib who had good performance status (ECOG 0‐1) and liver function (Child‐Pugh‐A). This study characterizes subsequent treatments received by HCC patients after sorafenib, and determines the proportion of patients eligible for novel therapies if strict eligibility criteria (SEC) were utilized compared to more liberal modified eligibility criteria (MEC, including ECOG 2, Child‐Pugh‐B7). Methods HCC patients who received sorafenib between 2008 and 2017 were included from the Canadian HCC CHORD Database. Patients were classified as eligible or ineligible based on available CELESTIAL, RESORCE, and REACH‐2 trial SEC or MEC. Median overall survival (mOS) was assessed using the Kaplan‐Meier method. Results A total of 730 patients were identified; and 172 (23.6%) received subsequent treatment. Patients who received subsequent treatment had longer mOS than those who did not (12.1 vs 3.3 months; P < .001). Using SEC, only 13.1% of patients would be eligible for cabozantinib, regorafenib, or ramucirumab. Expanding eligibility to include patients who meet MEC increased the proportion of eligible patients to 31.7%. Higher ineligibility for regorafenib and ramucirumab was driven by trial‐specific criteria, including sorafenib intolerance (28%) for RESORCE and AFP <400 (58.9%) for REACH‐2. Conclusions A small proportion of real‐world HCC patients would be eligible for cabozantinib, regorafenib, or ramucirumab if SEC in clinical trials were followed, while more than double would be eligible if MEC were applied. Patients who received subsequent treatment had improved mOS, regardless of whether they met SEC or MEC.https://doi.org/10.1002/cam4.3116cabozantinibhepatocellular carcinomaramucirumabregorafenibtrial eligibility
spellingShingle Andrea S. Fung
Vincent C. Tam
Daniel E. Meyers
Hao‐Wen Sim
Jennifer J. Knox
Valeriya Zaborska
Janine Davies
Yoo‐Joung Ko
Eugene Batuyong
Haider Samawi
Winson Y. Cheung
Richard Lee‐Ying
Second‐line treatment of hepatocellular carcinoma after sorafenib: Characterizing treatments used over the past 10 years and real‐world eligibility for cabozantinib, regorafenib, and ramucirumab
Cancer Medicine
cabozantinib
hepatocellular carcinoma
ramucirumab
regorafenib
trial eligibility
title Second‐line treatment of hepatocellular carcinoma after sorafenib: Characterizing treatments used over the past 10 years and real‐world eligibility for cabozantinib, regorafenib, and ramucirumab
title_full Second‐line treatment of hepatocellular carcinoma after sorafenib: Characterizing treatments used over the past 10 years and real‐world eligibility for cabozantinib, regorafenib, and ramucirumab
title_fullStr Second‐line treatment of hepatocellular carcinoma after sorafenib: Characterizing treatments used over the past 10 years and real‐world eligibility for cabozantinib, regorafenib, and ramucirumab
title_full_unstemmed Second‐line treatment of hepatocellular carcinoma after sorafenib: Characterizing treatments used over the past 10 years and real‐world eligibility for cabozantinib, regorafenib, and ramucirumab
title_short Second‐line treatment of hepatocellular carcinoma after sorafenib: Characterizing treatments used over the past 10 years and real‐world eligibility for cabozantinib, regorafenib, and ramucirumab
title_sort second line treatment of hepatocellular carcinoma after sorafenib characterizing treatments used over the past 10 years and real world eligibility for cabozantinib regorafenib and ramucirumab
topic cabozantinib
hepatocellular carcinoma
ramucirumab
regorafenib
trial eligibility
url https://doi.org/10.1002/cam4.3116
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