scholarly journals Long-lasting remission in a metastatic hepatocellular carcinoma patient after combined regorafenib therapy and surgery

2020 ◽  
Vol 7 (3) ◽  
pp. HEP24
Author(s):  
Elisabetta Goio ◽  
Luca Ielasi ◽  
Francesca Benevento ◽  
Matteo Renzulli ◽  
Francesco Tovoli

Aims: The therapeutic scenario of systemic treatments for hepatocellular carcinoma (HCC) is rapidly changing. There is much interest in the possibility of combining new therapies with surgery, but clinical data is lacking. We aimed to provide an example of such integration. Patients & methods: We report a patient with metastatic HCC who received regorafenib in the setting of the RESORCE trial. Results: A brilliant response led to a tumor downstaging and a subsequent adrenal metastasectomy with radical intent. Conclusions: New agents will change the therapeutic perspectives in advanced HCC and lead to a higher rate of objective responses, with possibilities of associating systemic therapy and surgery. Thus, the management of HCC will require more and more of an integrated, multidisciplinary and personalized approach.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 279-279
Author(s):  
Arjun Gupta ◽  
Allicia C Girvan ◽  
Kristin M Sheffield ◽  
Yongmei Chen ◽  
Kelly Rae Kirsch ◽  
...  

279 Background: Several therapies have recently gained regulatory approval in the United States (US) as second-line (2L) treatment options for patients with advanced unresectable or metastatic hepatocellular carcinoma (HCC). Treatment patterns and associated outcomes in a real-world population, especially in the contemporary era, remain understudied. Methods: This retrospective study utilized electronic health record data collected during routine patient care in outpatient oncology practices in the US. Adult patients diagnosed with advanced/ metastatic HCC between April 2017 and January 2020 were identified from the Concerto HealthAI database. Patients who survived at least one month from the end of first-line (1L) systemic therapy but did not initiate 2L therapy were classified as having received supportive care alone (SCA). Demographics, patient and disease characteristics, treatment patterns, and outcomes were described descriptively. Median overall survival (OS) from initiation of 2L therapy or end of 1L therapy for patients receiving SCA until death was estimated by the Kaplan-Meier method. Results: A total of 586 patients with advanced/ metastatic HCC were identified in the database. 330 patients received 1L therapy, and of those patients 63% (N= 207) received systemic 2L therapy (n= 105) or SCA (n= 102). At first diagnosis of advanced/ metastatic HCC, the median age was 64 years, and 86% were male. Of patients with ECOG status available at diagnosis (67%), 45% had ECOG status 0-1. The most common 1L agents prescribed were sorafenib (n= 126, 61%), lenvatinib (n= 28,14%) and sorafenib + nivolumab (n= 13, 6%) The most frequent agents prescribed in 2L were nivolumab (n= 44, 42%), sorafenib (n=18,17%), and lenvatinib (n=9, 9%). The median OS of patients receiving any systemic 2L therapy was 7.7 months (95% confidence interval 5.7-11.1) from time of receiving 2L therapy, whereas the median OS of patients receiving SCA was 5.0 months (95% confidence interval 3.3-7.1) from time of end of 1L therapy. Conclusions: In this contemporary national real-world cohort of patients with advanced/ metastatic HCC, a third of patients who received 1L therapy subsequently received 2L therapy. Next steps include investigating factors associated with non-receipt of 2L therapy, sequencing of therapies when multiple lines of therapies are received, and evaluating outcomes by type of agent received in 2L and beyond.


2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 288-288
Author(s):  
Jean-frederic Blanc ◽  
Caroline Laurendeau ◽  
Nadia Kelkouli ◽  
Philippe Mathurin

288 Background: The prognosis for patients with late-stage hepatocellular carcinoma (HCC) is poor, with only one systemic treatment option available for patients until 2017. Aim: To describe treatment patterns and survival of French patients following diagnosis of late-stage HCC (Barcelona Clinic Liver Cancer classification B, C or D), using a comprehensive nationwide claims database, SNDS. Methods: The SNDS database was searched from 1 January 2015 to 31 December 2017 for patients with a diagnosis of HCC (ICD-10: C220) and late-stage disease, defined by the identification of transcatheter arterial chemoembolization (TACE) or radioembolization (TARE), HCC systemic therapy and/or best supportive care (BSC). Patients were followed up for a maximum of 2 years. Results: 17,298 patients (mean age: 68.7 years (SD: 11.3), 82.6% male) were identified, with 72.4% diagnosed at late stage. During follow-up, 29.6% of patients were treated with TACE or TARE, and 27.1% received systematic therapy (sorafenib in 99.5% of cases). The median duration of systemic treatment was 7.9 (95% CI: 7.4-8.5) months. In 62.5% of cases, this treatment was discontinued at 12 months; this proportion fell to 40.3% when using mortality as a competitive risk. Survival since diagnosis of late stage HCC differed according to the type of first treatment received. Median overall survival was 23.7, 11.9, 7.4 and 1 month in patients initially receiving TACE, TARE, systemic therapy or no treatment, respectively. Conclusions: These results confirm the high clinical burden of late-stage HCC over this period and the need for second-line systemic treatments to improve patient outcomes.


2020 ◽  
Vol 20 (2) ◽  
pp. 84-99
Author(s):  
Chen-Hao Zhang ◽  
Ming Li ◽  
You-Pei Lin ◽  
Qiang Gao

The majority of patients with hepatocellular carcinoma (HCC) are diagnosed at an advanced stage that can only benefit from systemic treatments. Although HCC is highly treatmentresistant, significant achievements have been made in the molecular targeted therapy and immunotherapy of HCC. In addition to regorafenib, cabozantinib and ramucirumab were approved for the second- line targeted treatment by the FDA after disease progression on sorafenib. Nivolumab failed to demonstrate remarkable benefit in overall survival (OS) as first-line therapy, while pembrolizumab did not achieve pre-specified statistical significance in both OS and progression-free survival (PFS) as second-line treatment. Combinations of targeted agents, immune checkpoint inhibitors and other interventions showed favorable results. In this review, we summarized the progress of systemic therapy in HCC and discussed the future directions of the treatment of HCC.


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15632-e15632 ◽  
Author(s):  
Z. Lin ◽  
D. Chang ◽  
Y. Shao ◽  
C. Hsu ◽  
C. Hsu ◽  
...  

e15632 Background: Hepatocellular carcinoma (HCC) is a common malignant disease. Promising results of prospective clinical trials using systemic therapy for patients with advanced HCC are emerging. The aim of this study was to explore prognostic factors of survival in advanced HCC patients eligible for clinical trials of systemic therapy. Methods: From December 1990 to July 2005, 236 patients with unresectable HCC were enrolled into 6 phase II trials of systemic therapy using the following regimens: (1) oral etoposide + tamoxifen, (2)doxorubicin + tamoxifen, (3)IFN-α2b + doxorubicin + tamoxifen, (4)pegylated liposomal doxorubicin, (5)thalidomide, and (6)arsenic trioxide. Univariate and multivariate analyses of 23 relevant clinical characteristics/staging systems were used to identify prognostic factors of survival. Results: Baseline characteristics: median age 55; male/female: 192/44; HBsAg(+) 71%; anti-HCV(+) 30%; Okuda stage I/II/III: 42%/55%/3%; AJCC stage III/IV: 30%/61%; BCLC stage B/C/D: 1%/94%/5%; CLIP score 0–3/4–6: 70%/30%; portal vein thrombosis 53%; extrahepatic metastasis 59%; prior chemoembolization 46%. The objective response rate according to WHO criteria was 11.4%. The median overall survival was 118 days (95% CI, 103–133). In the multivariate analysis, significant predictors of a shorter overall survival were: HBsAg(+) with a hazard ratio (HR) = 1.808 (95% CI, 1.121–2.916; P= 0.015), symptomatic with HR = 1.745 (95% CI, 1.072–2.840; P= 0.025), ECOG≥2 with HR = 1.763 (95% CI, 1.040–2.988; P= 0.035), and high BCLC stage with HR = 3.282 (95% CI, 1.129–9.541; P= 0.029). Conclusions: Patients with advanced HCC who are eligible for systemic therapeutic trials have patient- and disease-related prognostic factors. Positive HBsAg, symptomatic, ECOG performance≥2, and high BCLC stage predict a shorter overall survival. No significant financial relationships to disclose.


Cancers ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 861 ◽  
Author(s):  
Kehua Zhou ◽  
Christos Fountzilas

Hepatocellular carcinoma (HCC) is one of the most commonly diagnosed cancers worldwide; most patients are diagnosed with advanced disease for which there is no known cure. Tremendous progress has been made over the past decade in the development of new agents for HCC, including small-molecule kinase inhibitors such as sorafenib, lenvatinib, cabozantinib, regorafenib, and monoclonal antibodies like ramucirumab, nivolumab, and pembrolizumab. Ideal use of these agents in clinics has improved the long-term outcome of patients with advanced HCC as well as introduced unique toxicities that can affect quality of life. These toxicities usually are thought to be partially related to cirrhosis, a major risk factor for the development of HCC and a pathophysiological barrier complicating the optimal delivery of antineoplastic therapy. Additionally, side effects of medications together with advanced HCC symptoms not only decrease quality of life, but also cause treatment interruptions and dose reductions that can potentially decrease efficacy. Physicians caring for patients with advanced HCC are called to optimally manage HCC along with cirrhosis in order to prolong life while at the same time preserve the quality of life. In this review, we aimed to summarize outcomes and quality of life with the use of modern systemic treatments in advanced HCC and provide a physician reference for treatment toxicity and cirrhosis management.


2018 ◽  
pp. 27-32
Author(s):  
V. V. Breder ◽  
M. U. Pitkevich ◽  
E. R. Virshke ◽  
L. A. Kostyakova ◽  
I. A. Dzhanyan ◽  
...  

Choice of the optimal therapy for BCLC-B hepatocellular carcinoma (HCC) is a significant clinical problem. Transarterial chemoembolisation (TACE) is considered to be the method of choice as this approach is reported to produce a direct effect and to have a significant survival rate. However, TACE is not always applicable and produce a survival benefit due to the clinical heterogeneity of BCLC-B HCC. The article includes different approaches for BCLC-B HCC patients, TACE prediction and refractory criteria as well as the results obtained. The necessity of timely sorafenib systemic therapy in BCLC-B and in advanced HCC after TACE is discussed. Practical application of regorafenib as the second line in HCC systemic treatment is discussed.


2015 ◽  
Vol 33 (3_suppl) ◽  
pp. TPS496-TPS496 ◽  
Author(s):  
Ghassan K. Abou-Alfa ◽  
Ann-Lii Cheng ◽  
Tim Meyer ◽  
Anthony B. El-Khoueiry ◽  
Masafumi Ikeda ◽  
...  

TPS496 Background: Currently, there are no approved systemic therapies for patients with advanced hepatocellular carcinoma (HCC) who fail sorafenib. Cabozantinib is an oral receptor tyrosine kinase inhibitor (TKI) with activity against tyrosine kinases including MET, RET and VEGFRs. MET and VEGFR signaling have been implicated in tumor neo-angiogenesis and invasion. MET is overexpressed in HCC compared with non-tumor liver tissue, with higher MET expression linked to poor prognosis. Cabozantinib prolonged survival in a MET-driven transgenic mouse model of HCC, and has demonstrated clinical activity in multiple solid tumor types, including 41 subjects with advanced HCC treated in a phase 2 randomized discontinuation study. Methods: This phase 3, randomized, double-blind study evaluates the efficacy and safety of cabozantinib compared with placebo in subjects with advanced HCC previously treated with sorafenib and have progressed following 1-2 prior systemic treatments for HCC. Subjects must be ≥ 18 year old, have Child-Pugh Score of A and ECOG PS ≤ 1. Subjects are randomized 2:1 to receive either cabozantinib or placebo. Stratification factors are etiology of disease, geographic region and the presence of extrahepatic spread of disease and/or macrovascular invasion. The primary endpoint is overall survival. Secondary endpoints are progression-free survival and objective response rate by RECIST 1.1. Additional endpoints include safety, tolerability, circulating tumor cells, serum bone markers and plasma biomarkers, effects on bony disease assessed by bone scan and health-related quality of life (HRQoL) using the EuroQol Health questionnaire (EQ-5D-5L). Enrollment was initiated in September 2013. Target recruitment is 760 subjects. A total of 621 events planned with 2 interim analyses (at 311 and 466 events) would provide 90% power to detect a 31.6% increase in OS (HR=0.76). Clinical trial information: NCT01908426.


2020 ◽  
Vol 27 (29) ◽  
pp. 4789-4805 ◽  
Author(s):  
Melissa Frizziero ◽  
Mairéad G. McNamara ◽  
Angela Lamarca ◽  
Rille Pihlak ◽  
Roopa Kurup ◽  
...  

Hepatocellular carcinoma (HCC) is a frequent and increasing cause of cancerrelated deaths worldwide. Reversing this trend is complicated by the varied aetiological factors leading to liver cirrhosis resulting in molecular genetic and clinical heterogeneity, combined with frequent presentation at advanced stage. Large-scale genomic studies have identified alterations in key signalling pathways for HCC development and progression, but these findings have not yet directly influenced patient management in the clinical setting. Despite these translational challenges, a small number of anti-angiogenic systemic therapy agents have succeeded in recent randomized trials enriching the repertoire of available treatments for advanced HCC. In addition, the early promise of immune checkpoint inhibition is now on the cusp of delivering changes to standard systemic therapy algorithms. This review focuses on recent translational and clinical developments that have advanced current practice and explores the challenges encountered in attempting to improve the outcomes and experience of patients diagnosed with advanced HCC.


2020 ◽  
Vol 37 (05) ◽  
pp. 466-474
Author(s):  
Hanna Javan ◽  
Farshid Dayyani ◽  
Nadine Abi-Jaoudeh

AbstractTreatment of advanced hepatocellular carcinoma (HCC) is challenging. Several randomized clinical trials are investigating the efficacy of systemic therapy, immunotherapy, and locoregional therapy as monotherapy or combined with other modalities in the treatment of HCC. Systemic therapy is the preferred treatment in advanced disease. To date, multiple first-line and second-line agents received Food and Drug Administration approval. For over a decade, sorafenib was the only first-line agent. In May 2020, combination of atezolizumab and bevacizumab has been approved as a first-line systemic regimen. Lenvatinib is another first-line agent that has multikinase activity. Second-line agents include cabozantinib, regorafenib, ramucirumab, and nivolumab. Adoptive cell transfer therapy is a highly specific immunotherapy that has shown antitumor activity against HCC. Oncolytic viruses are genetically modified viruses that infect cancer cells and induce apoptosis. Locoregional therapies such as transarterial chemoembolization and radioembolization have shown a potential benefit in selected patients with advanced HCC. In this review, we aim to summarize the treatment options available for advanced HCC.


Sign in / Sign up

Export Citation Format

Share Document