scholarly journals Clinical Outcomes with Multikinase Inhibitors after Progression on First-Line Atezolizumab plus Bevacizumab in Patients with Advanced Hepatocellular Carcinoma: A Multinational Multicenter Retrospective Study

Liver Cancer ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 107-114
Author(s):  
Changhoon Yoo ◽  
Jwa Hoon Kim ◽  
Min-Hee Ryu ◽  
Sook Ryun Park ◽  
Danbi Lee ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Retrospective Study ◽  
Disease Progression ◽  
Clinical Outcomes ◽  
Systemic Therapy ◽  
Advanced Hepatocellular Carcinoma ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Advanced Hcc

<b><i>Introduction:</i></b> Atezolizumab-bevacizumab is the new standard of care for first-line treatment of advanced hepatocellular carcinoma (HCC). However, the optimal sequence of therapy after disease progression on atezolizumab-bevacizumab is unclear. <b><i>Methods:</i></b> This multinational, multicenter, and retrospective study assessed clinical outcomes of patients with advanced HCC who received subsequent systemic therapy after progression on atezolizumab-bevacizumab between July 2016 and April 2019. <b><i>Results:</i></b> Among 71 patients treated with atezolizumab-bevacizumab, a total of 49 patients who received subsequent systemic therapy were included in this analysis; the median age was 60 years (range, 37–80) and 73.5% were male. All patients were classified as Child-Pugh A and Barcelona-Clinic Liver Cancer stage C. Multikinase inhibitors (MKIs), including sorafenib (<i>n</i> = 29), lenvatinib (<i>n</i> = 19), and cabozantinib (<i>n</i> = 1), were used as second-line therapy for all patients. The objective response rate and disease control rate were 6.1 and 63.3%, respectively, in all patients. With a median follow-up duration of 11.0 months, median progression-free survival (PFS) and overall survival (OS) were 3.4 months (95% confidence interval [CI] 1.8–4.9) and 14.7 months (95% CI 8.1–21.2) in all patients. Median PFS with lenvatinib was significantly longer than that with sorafenib (6.1 vs. 2.5 months; <i>p</i> = 0.004), although there was no significant difference in median OS (16.6 vs. 11.2 months; <i>p</i> = 0.347). Treatment-related adverse events (TRAEs) of any grade and grade 3 occurred in 42 (85.7) and 8 (16.3%) of patients. Common TRAEs included hand-foot syndrome (<i>n</i> = 26, 53.1%), fatigue (<i>n</i> = 14, 28.6%), hypertension (<i>n</i> = 14, 28.6%), and diarrhea (<i>n</i> = 12, 24.5%). <b><i>Conclusion:</i></b> Second-line treatment with MKIs, mostly sorafenib and lenvatinib, showed comparable efficacy and manageable toxicities in patients with advanced HCC after disease progression on atezolizumab-bevacizumab.

Clinical outcomes with multikinase inhibitors after progression on first-line atezolizumab plus bevacizumab in patients with advanced hepatocellular carcinoma: A multinational, multicenter retrospective study.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 272-272
Author(s):  
Changhoon Yoo ◽  
Jwa Hoon Kim ◽  
Min-Hee Ryu ◽  
Sook Ryun Park ◽  
Joycelyn Jie Xin Lee ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Retrospective Study ◽  
Disease Progression ◽  
Clinical Outcomes ◽  
Advanced Hepatocellular Carcinoma ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Advanced Hcc ◽  
Multikinase Inhibitors

272 Background: Atezolizumab-bevacizumab is the new standard of care for first-line treatment of advanced hepatocellular carcinoma (HCC). However, the optimal sequence of therapy after disease progression on atezolizumab-bevacizumab is unclear. Methods: This multinational, multicenter, retrospective study assessed clinical outcomes of patients with advanced HCC who received subsequent systemic therapy after progression on atezolizumab-bevacizumab in Korea, Hong Kong and Singapore between July 2016 and April 2019. Results: A total of 49 patients were included; the median age was 60 years (range, 3780) and 73.5% were male. All patients were classified as Child-Pugh A and Barcelona-Clinic Liver Cancer stage C. Multikinase inhibitors (MKIs), including sorafenib (n = 29), lenvatinib (n = 19), and cabozantinib (n = 1), were used as second-line therapy for all patients. The objective response rate (ORR) and disease control rate (DCR) were 6.1% and 63.3%, respectively, in all patients. With a median follow-up duration of 11.0 months, median progression-free survival (PFS) and overall survival (OS) were 3.4 months (95% confidence interval [CI] 1.84.9) and 14.7 months (95% CI 8.121.2) in all patients. Median PFS with lenvatinib was significantly longer than that with sorafenib (6.1 months vs. 2.5 months; P= 0.004), although there was no significant difference in median OS (16.6 months vs. 11.2 months; P= 0.347). Treatment-related adverse events (TRAEs) of any grade and grade 3 occurred in 42 (85.7%) and 8 (16.3%) of patients. Common TRAEs included hand-foot syndrome (HFS) (n = 26, 53.1%), fatigue (n = 14, 28.6%), hypertension (n = 14, 28.6%), and diarrhea (n = 12, 24.5%). Conclusions: Second-line treatment with MKIs, mostly sorafenib and lenvatinib, showed comparable efficacy and manageable toxicities in patients with advanced HCC after disease progression on atezolizumab-bevacizumab.

scholarly journals Posttreatment after lenvatinib in patients with advanced hepatocellular carcinoma.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 278-278
Author(s):  
Keisuke Koroki ◽  
Naoya Kanogawa ◽  
Susumu Maruta ◽  
Sadahisa Ogasawara ◽  
Masamichi Obu ◽  
...  
Keyword(s):  
Systemic Therapy ◽  
Advanced Hepatocellular Carcinoma ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Radiological Progression ◽  
Advanced Hcc ◽  
Line Therapy ◽  
Pugh Class ◽  
Third Line

278 Background: In clinical practice, the major disadvantage of lenvatinib to treat advanced hepatocellular carcinoma (HCC) is the lack of a posttreatment agent that has shown clear effectiveness. Thus, the establishment of second-line treatment after lenvatinib treatment failure is an urgent clinical issue to be addressed in systemic therapy in patients with advanced HCC. The study used real-world clinical data to explore candidate drugs that might be appropriate as second-line treatment after lenvatinib. Methods: We retrospectively reviewed the medical records of all patients with advanced HCC who received lenvatinib as the first-line agent in seven institutions in Japan between 23 March 2018 and 31 September 2019. Results: During the study period, 178 patients with advanced HCC received lenvatinib as first-line systemic therapy. At the time of lenvatinib administration, most patients were Eastern Cooperative Oncology Group Performance Status grade 0 or 1 (94.9%) and Child–Pugh class A (84.3%). According to the baseline radiological assessments, 25.3% and 36.0% of patients had macrovascular invasion and extrahepatic metastasis, respectively. Overall survival and progression-free survival (PFS) for lenvatinib treatment were 13.3 months (95% CI: 11.5–15.2) and 6.7 months (95% CI: 5.1–8.3), respectively. Of the 151 patients who discontinued lenvatinib, 71 (47.0%) converted to posttreatment. The conversion rates from lenvatinib to a second-line agent and from a second-line agent to a third-line agent were 41.4% and 42.4%, respectively. Based on multivariate analysis, lenvatinib response was defined as complete or partial according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST). Lenvatinib discontinuation due to radiological progression, according to mRECIST, was associated with a significantly higher probability of conversion to posttreatment after lenvatinib. Of the 63 patients who received second-line systemic therapy, 53 (84.1%) were administered sorafenib, with a PFS, response rate (RR), and disease control rate (DCR) of 1.8 months (95% CI: 0.6–3.0), 1.8%, and 20.8%, respectively. According to the Cox proportional hazards regression model, lenvatinib discontinuation due to radiological progression, Child–Pugh class B, and intrahepatic tumor volume > 50% at the time of sorafenib administration significantly contributed to a shorter PFS. Of the 22 patients who received regorafenib after lenvatinib discontinuation, five cases were as second-line therapy, and 17 were as third-line therapy. PFS, RR, and DCR for regorafenib treatment were 3.2 months (range, 1.5–4.9 months), 13.6%, and 36.3%, respectively. Conclusions: Sorafenib was not considered a candidate posttreatment agent after lenvatinib, except in a limited number of patients who discontinued lenvatinib without radiological progression. Regorafenib is a potential posttreatment agent after lenvatinib.

scholarly journals Therapy in Advanced Hepatocellular Carcinoma

2020 ◽  
Vol 37 (05) ◽  
pp. 466-474
Author(s):  
Hanna Javan ◽  
Farshid Dayyani ◽  
Nadine Abi-Jaoudeh
Keyword(s):  
Hepatocellular Carcinoma ◽  
Systemic Therapy ◽  
Randomized Clinical Trials ◽  
Adoptive Cell Transfer ◽  
Oncolytic Viruses ◽  
Locoregional Therapy ◽  
Advanced Hepatocellular Carcinoma ◽  
Second Line ◽  
First Line ◽  
Advanced Hcc

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.

scholarly journals Predictive and Prognostic Factors in HCC Patients Treated with Sorafenib

Medicina ◽  
2019 ◽  
Vol 55 (10) ◽  
pp. 707 ◽  
Author(s):  
Oronzo Brunetti ◽  
Antonio Gnoni ◽  
Antonella Licchetta ◽  
Vito Longo ◽  
Angela Calabrese ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Prognostic Factors ◽  
Prognostic Markers ◽  
Kinase Inhibitor ◽  
Quality Standard ◽  
Advanced Hepatocellular Carcinoma ◽  
Line Treatment ◽  
First Line ◽  
Advanced Hcc ◽  
First Line Treatment

Sorafenib is an oral kinase inhibitor that enhances survival in patients affected by advanced hepatocellular carcinoma (HCC). According to the results of two registrative trials, this drug represents a gold quality standard in the first line treatment of advanced HCC. Recently, lenvatinib showed similar results in terms of survival in a non-inferiority randomized trial study considering the same subset of patients. Unlike other targeted therapies, predictive and prognostic markers in HCC patients treated with sorafenib are lacking. Their identification could help clinicians in the daily management of these patients, mostly in light of the new therapeutic options available in the first.

scholarly journals Role of immunotherapy in the management of hepatocellular carcinoma: current standards and future directions

2020 ◽  
Vol 27 (S3) ◽  
Author(s):  
A. Weinmann ◽  
P.R. Galle
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Clinical Trials ◽  
Statistical Significance ◽  
Phase Iii ◽  
Advanced Hepatocellular Carcinoma ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Promising Therapeutic Approach

 The multikinase inhibitor sorafenib was the only approved systemic therapy in advanced hepatocellular carcinoma (hcc) for about a decade. In recent years, the number of approved agents has increased significantly as a result of a number of positive phase iii clinical trials. Lenvatinib as a first-line treatment, and regorafenib, cabozantinib, and ramucirumab in the second-line setting are now approved by the U.S. Food and Drug Administration (fda) and the European Medicines Agency. In phase ii studies, immunotherapy with nivolumab and monotherapy using pembrolizumab yielded impressive results for overall survival in therapy-naïve and pretreated patients, leading to the accelerated approval by the fda of nivolumab and pembrolizumab for second-line treatment. However, phase iii trials of nivolumab in the first line and pembrolizumab in the second line as single agents failed to reach statistical significance, although clinical benefit for a subset of patients with long durations of response could be demonstrated. Despite that setback, immunotherapy for hcc is a promising therapeutic approach, and the combination of immunotherapy with other treatment modal­ities such as monoclonal antibodies, tyrosine kinase inhibitors, or local therapies has the potential to increase the overall response rate and survival. Recently, the results of a phase iii trial of combination atezolizumab–bevacizumab compared with sorafenib showed a highly significant survival benefit and median overall survival that was not reached in the immunotherapy arm, making the combination the preferred standard of care in first-line therapy. Despite the impressive results and generally good toxicity profile of immunotherapy, patients who respond to therapy constitute only a subset of the overall population, and response rates are still limited. This review focuses on the currently reported results and ongoing clinical trials of checkpoint inhibitor–based immunotherapy in hcc.

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