Outcomes of sequential treatment with sorafenib followed by regorafenib for HCC: Additional analyses from the phase III RESORCE trial

Finn, Richard S.; Merle, Philippe; Granito, Alessandro; Huang, Yi Hsiang; Bodoky, G.; Pracht, Marc; Yokosuka, Osamu; Rosmorduc, Olivier; Gerolami, René; Caparello, Chiara; Cabrera, Roniel; Chang, Charissa; Sun, Weijing; LeBerre, M.-A.; Baumhauer, Annette; Meinhardt, Gerold; Bruix, Jordi

doi:10.1016/j.jhep.2018.04.010

Cited by 282 publications

(264 citation statements)

References 15 publications

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“…In the present study, Child–Pugh A5 at sorafenib initiation was a significant factor related to eligibility for second‐line therapy and good OS. In the results of the RESORCE trial, the OS of patients with Child–Pugh A5 was significantly longer than that in patients with Child–Pugh A6 . Therefore, in order to increase the number of Child–Pugh A5 patients in whom sorafenib treatment can be introduced, it is important that BCLC stage B patients be switched to sorafenib as soon as transarterial chemoembolization is judged as ineffective, while their Child–Pugh score remains at 5 .…”

Section: Discussionmentioning

confidence: 99%

Clinical characteristics and outcomes of candidates for second‐line therapy, including regorafenib and ramucirumab, for advanced hepatocellular carcinoma after sorafenib treatment

Kuzuya

Ishigami

Ito

et al. 2019

Hepatology Research

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Aim This study aimed to investigate the clinical characteristics and outcomes of candidates for second‐line therapy, including regorafenib and ramucirumab, for advanced hepatocellular carcinoma (HCC) after sorafenib treatment. Methods Of 122 patients, 103 were radiologically confirmed as progressive disease (PD) (sorafenib‐refractory group), and 19 discontinued sorafenib therapy due to adverse events prior to radiologic PD (sorafenib‐intolerant group). Patients in the sorafenib‐refractory group were divided into two subgroups each, according to their eligibility for second‐line treatment (second‐line‐in and ‐out group), regorafenib (RESORCE‐in and ‐out group), or ramucirumab (REACH‐2‐in and ‐out group). Results Patients included in the non‐candidate group were those with α‐fetoprotein level <400 ng/mL (n = 51, 49.5%), daily sorafenib dose <400 mg (n = 44, 42.7%), Child–Pugh B or C (n = 40, 38.8%), and Eastern Cooperative Oncology Group performance status score ≥2 (n = 24, 23.3%). The percentages of candidates were 57.3% for second‐line, 35.0% for regorafenib, and 23.3% for ramucirumab. The median post‐progression survival (PPS) was significantly longer for the second‐line‐in and the RESORCE‐in groups than in the non‐candidate groups (12.6 and 11.0 months vs. 3.0 and 6.1 months, respectively). The PPS was not significantly different between the REACH‐2‐in and ‐out groups. A significant predictor of candidates for second‐line treatment at sorafenib initiation was a Child–Pugh score of 5 (A5). Conclusions Not all patients refractory to sorafenib were candidates for second‐line therapy. A Child–Pugh score of A5 at sorafenib initiation was an important and favorable factor related to eligibility for second‐line therapy and good outcomes.

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Section: Discussionmentioning

confidence: 99%

Clinical characteristics and outcomes of candidates for second‐line therapy, including regorafenib and ramucirumab, for advanced hepatocellular carcinoma after sorafenib treatment

Kuzuya

Ishigami

Ito

et al. 2019

Hepatology Research

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“…However, it is worth stating that this positive outcome is only possible in those patients who are able to receive regorafenib as a second‐line treatment. The survival benefit of regorafenib was independent from the last dose of sorafenib (800 mg/day versus <800 mg/day but ≥400 mg/day) . This estimation is widely variable depending mostly on the pattern of progression, when regorafenib treatment is started, and on the development of early dermatologic AEs under sorafenib and regorafenib .…”

Section: Second‐line Treatmentsmentioning

confidence: 99%

New Systemic Treatments in Advanced Hepatocellular Carcinoma

2019

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The principal advancements in the treatment of hepatocellular carcinoma (HCC) are the use of new systemic treatments, such as lenvatinib in first‐line treatment and regorafenib, cabozantinib, and ramucirumab in second‐line treatment, because of their benefits in terms of overall survival. In addition, nivolumab as a second‐line agent was approved by the US Food and Drug Administration in 2017 based on improved radiological response data. Physicians and patients alike will greatly benefit from this expanded arsenal of treatments once all these new drugs for the treatment of HCC finally become available. Unfortunately, in our review of the available data, we found a conspicuous lack of approved systemic treatments for HCC in the distinct setting of after liver transplantation (LT). Careful evaluation of the clinical trials for approved systemic treatments of HCC is crucial when considering the best options for those with HCC recurrence after LT. Although several first‐line or second‐line treatments have been shown to be effective for HCC, each of these trials was composed of its own specific populations, and those with HCC recurrence after LT were excluded. We have also summarized from a critical and clinical point of view the issues involved in the management of patients who are candidates for systemic treatment in this era of multiple drugs for the same indication.

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“…Regorafenib demonstrated a significant survival benefit compared to placebo (10.7 vs 7.8 months, HR 0.63, 95% CI 0.50‐0.79), with a consistent benefit across all examined subgroups. Regorafenib was also noted to provide consistent benefit to patients regardless of rate of progression during sorafenib treatment and timing of last sorafenib dose prior to regorafenib initiation . Second endpoints included improvements in time to progression (3.2 vs 1.5 months) and objective response rates (11% vs 4%, P = .005).…”

Section: Second Line Therapiesmentioning

confidence: 99%

Review article: new therapeutic interventions for advanced hepatocellular carcinoma

Bangaru

Marrero

Singal

2019

Aliment Pharmacol Ther

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Summary Background Advanced hepatocellular carcinoma (HCC) portends a poor prognosis; however recent advances in first‐line and second‐line treatment options should yield significant improvements in survival. Aim To summarize the evolving landscape of treatment options for patients with advanced HCC. Methods We reviewed published clinical trials conducted in patients with advanced HCC published in PubMed or presented at national conferences. Results Sorafenib was approved for treatment of unresectable HCC in 2007 and remained the only therapy with proven survival benefit in advanced HCC for several years. Lenvatinib, another tyrosine‐kinase inhibitor, was recently shown to have non‐inferior survival vs sorafenib and is another first‐line treatment option. The tyrosine‐kinase inhibitors, regorafenib and cabozantinib, were shown to significantly improve survival in the second‐line setting after sorafenib failure. Ramucirumab, a VEGF inhibitor, can also improve survival in the second‐line setting among patients with AFP ≥ 400 ng/dL. Phase II data highlight potential durable objective responses with immune checkpoint inhibitors, prompting conditional FDA approval of nivolumab and pembrolizumab in the second‐line setting; however, recent phase III data have failed to demonstrate improved survival compared to other treatment options. Ongoing trials are evaluating combination immune checkpoint inhibitor and immune checkpoint inhibitors with tyrosine‐kinase inhibitors or VEGF inhibitors in hopes of further increasing objective responses and overall survival in this patient population. Conclusion There are several first‐line and second‐line therapeutic options available for patients with advanced HCC. Further studies are needed to determine how best to select between and sequence the growing number of therapeutic options.

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Outcomes of sequential treatment with sorafenib followed by regorafenib for HCC: Additional analyses from the phase III RESORCE trial

Cited by 282 publications

References 15 publications

Clinical characteristics and outcomes of candidates for second‐line therapy, including regorafenib and ramucirumab, for advanced hepatocellular carcinoma after sorafenib treatment

Clinical characteristics and outcomes of candidates for second‐line therapy, including regorafenib and ramucirumab, for advanced hepatocellular carcinoma after sorafenib treatment

New Systemic Treatments in Advanced Hepatocellular Carcinoma

Review article: new therapeutic interventions for advanced hepatocellular carcinoma

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