scholarly journals Ramucirumab in the second-line for patients with hepatocellular carcinoma and elevated alpha-fetoprotein: patient-reported outcomes across two randomised clinical trials

ESMO Open ◽  
2020 ◽  
Vol 5 (4) ◽  
pp. e000797
Author(s):  
Andrew X Zhu ◽  
Ryan D Nipp ◽  
Richard S Finn ◽  
Peter R Galle ◽  
Josep M Llovet ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Patient Reported Outcomes ◽  
Group Performance ◽  
Eastern Cooperative Oncology Group ◽  
Alpha Fetoprotein ◽  
Advanced Hepatocellular Carcinoma ◽  
Second Line ◽  
Advanced Hcc ◽  
Link Type ◽  
Patient Reported

BackgroundSymptoms of advanced hepatocellular carcinoma (HCC) represent a substantial burden for the patient and are important endpoints to assess when evaluating treatment. Patient-reported outcomes were evaluated in subjects with advanced HCC and baseline alpha-fetoprotein (AFP) ≥400 ng/mL treated with second-line ramucirumab.Patients and methodsPatients with AFP≥400 ng/mL enrolled in the REACH or REACH-2 phase 3 studies were used in this analysis. Eligible patients had advanced HCC, Child-Pugh A, Eastern Cooperative Oncology Group performance status 0/1 and prior sorafenib. Patients received ramucirumab 8 mg/kg or placebo once every 2 weeks. Disease-related symptoms and health-related quality of life (HRQoL) were assessed with the Functional Assessment of Cancer Therapy Hepatobiliary Symptom Index (FHSI)-8 and EuroQoL-5-Dimensions (EQ-5D) instruments, respectively. Time to deterioration (TTD) (≥3-point decrease in FHSI-8 total score;≥0.06-point decrease in EQ-5D score, from randomisation to first date of deterioration) was determined using Kaplan-Meier estimation and the Cox proportional hazards model. Both separate and pooled analyses for REACH AFP≥400 ng/mL and REACH-2 patients were conducted.ResultsIn the pooled population with AFP ≥400 ng/mL (n=542; ramucirumab, n=316; placebo, n=226), median TTD in FHSI-8 total score was prolonged with ramucirumab relative to placebo (3.3 vs 1.9 months; HR 0.725; (95% CI 0.559 to 0.941); p=0.0152), including significant differences in back pain (0.668; (0.497 to 0.899); p=0.0044), weight loss (0.699; (0.505 to 0.969); p=0.0231) and pain (0.769; (0.588 to 1.005); p=0.0248) symptoms. TTD in EQ-5D score was not significantly different between ramucirumab and placebo groups (median 2.9 vs 1.9 months). Results in the individual trials were consistent with these findings.ConclusionsRamucirumab in second-line treatment of advanced HCC demonstrates consistent benefit in the delay of deterioration in disease-related symptoms with no worsening of HRQoL. Taken with previously demonstrated ramucirumab-driven survival benefits in this setting, these data may inform patient–clinician discussions about the benefit–risk profile of this therapy.Trial registration numberNCT01140347; NCT02435433, NCT02435433.

Phase II Trial of the Combination of Bevacizumab and Erlotinib in Patients Who Have Advanced Hepatocellular Carcinoma

2009 ◽  
Vol 27 (6) ◽  
pp. 843-850 ◽  
Author(s):  
Melanie B. Thomas ◽  
Jeffrey S. Morris ◽  
Romil Chadha ◽  
Michiko Iwasaki ◽  
Harmeet Kaur ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Response Rate ◽  
Group Performance ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Evaluation Criteria ◽  
Progression Free Survival ◽  
Advanced Hepatocellular Carcinoma ◽  
Study Objective ◽  
Advanced Hcc

Purpose The study objective was to determine the proportion of patients with hepatocellular carcinoma (HCC) treated with the combination of bevacizumab (B) and erlotinib (E) who were alive and progression free at 16 weeks (16-week progression-free survival [PFS16]) of continuous therapy. Secondary objectives included response rate, median PFS, survival, and toxicity. Patients and Methods Patients who had advanced HCC that was not amenable to surgical or regional therapies, up to one prior systemic treatment; Childs-Pugh score A or B liver function; Eastern Cooperative Oncology Group performance status 0, 1, or 2 received B 10 mg/kg every 14 days and E 150 mg orally daily, continuously, for 28-day cycles. Tumor response was evaluated every 2 cycles by using Response Evaluation Criteria in Solid Tumors Group criteria. A total of 40 patients were treated. Results The primary end point of PFS16 was 62.5%. Ten patients achieved a partial response for a confirmed overall response rate (intent-to-treat) of 25%. The median PFSevent was 39 weeks (95% CI, 26 to 45 weeks; 9.0 months), and the median overall survival was 68 weeks (95% CI, 48 to 78 weeks; 15.65 months). Grades 3 to 4 drug-related toxicity included fatigue (n = 8; 20%), hypertension (n = 6; 15%), diarrhea (n = 4; 10%) elevated transaminases (n = 4; 10%), gastrointestinal hemorrhage (n = 5; 12.5%), wound infection (n = 2; 5%) thrombocytopenia (n = 1; 2.5%), and proteinuria, hyperbilirubinemia, back pain, hyperkalemia, and anorexia (n = 1 each). Conclusion The combination of B + E in patients who had advanced HCC showed significant, clinically meaningful antitumor activity. B + E warrant additional evaluation in randomized controlled trials.

Impact of Individual Components of the Metabolic Syndrome on the Outcome of Patients with Advanced Hepatocellular Carcinoma Treated with Sorafenib

2017 ◽  
Vol 36 (1) ◽  
pp. 78-88 ◽  
Author(s):  
Christian Labenz ◽  
Vera Prenosil ◽  
Sandra Koch ◽  
Yvonne Huber ◽  
Jens U. Marquardt ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Hepatocellular Carcinoma ◽  
Metabolic Syndrome ◽  
Group Performance ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Advanced Hepatocellular Carcinoma ◽  
Advanced Hcc ◽  
The Metabolic Syndrome ◽  
The Impact

Background/Aim: Individual components of the metabolic syndrome (MS) such as obesity or diabetes mellitus impair the prognosis of patients with hepatocellular carcinoma (HCC) following curative treatment approaches or transarterial therapies. The aim of this retrospective study was to assess the impact of these factors on the overall survival (OS) of patients with advanced HCC treated with sorafenib. Methods: Univariate and multivariate analyses were performed to assess the impact of individual components of the MS on the OS of 152 consecutive patients with advanced HCC treated with sorafenib. Results: The presence of overweight/obesity, type 2 diabetes mellitus, hypertension, dyslipidemia, and of the MS itself did not impair the median OS. Multivariate analysis showed that Eastern Cooperative Oncology Group Performance Status ≥1 (hazards ratio [HR] 2.03), presence of macrovascular invasion (HR 1.71), Child-Pugh score B/C (HR 2.19), tumor grading G3 (HR 2.17), no prior HCC treatment (HR 2.34), and the presence of 2 or more out of 5 individual components of the MS (HR 0.65) were independent prognostic factors regarding the median OS. Conclusions: Our investigations do not confirm a negative prognostic role of individual components of the MS or the MS itself for patients with advanced HCC treated with sorafenib.

Camrelizumab plus apatinib combined with TACE and cryoablation in the first-line treatment of advanced hepatocellular carcinoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. TPS4160-TPS4160
Author(s):  
Wenge Xing ◽  
Zhi Guo
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cancer ◽  
Combination Therapy ◽  
Group Performance ◽  
Objective Response ◽  
Eastern Cooperative Oncology Group ◽  
Enhancement Effect ◽  
Advanced Hepatocellular Carcinoma ◽  
Advanced Hcc ◽  
History Of

TPS4160 Background: Hepatocellular carcinoma (HCC) is a common cancer in the world, a leading cause of cancer-related death, and especially in China. Most of the HCC patients are diagnosed at an advanced stage and require a multidisciplinary approach. The IMbrave 50 trial has reported the successful efficacy of atezolizumab and bevacizumab combination therapy in advanced hepatocellular carcinoma, which indicate the potential efficacy of combination of immunotherapy and antiangiogenesis therapy in HCC patients. In some studies, the combinatorial approaches with immunotherapy and liver directed therapies such as transarterial chemoembolization (TACE), radiofrequency ablation (RFA), microwave ablation (MWA), and cryoablation are explored. Most combined interventional therapies reveal their enormous advantages as compared with any single therapeutic regimen alone, which may result from the immunologic enhancement effect of the multimodel therapy. In this study, we evaluated the efficacy and safety of combined therapy with camrelizumab plus apatinib mesylate and TACE plus cryoablation in patients with advanced HCC. Methods: This study was an open-label, single-arm, single centre, phase 2 trial in patients who were diagnosed with advanced HCC. Patients who meet the following criterias will be enrolled: (1) 18 - 75 years old; (2) Child-Pugh classification A or B(≤7);(3) Barcelona Clinic Liver Cancer stage B or C, or China liver cancer staging (CNLC) stage IIb̃IIIa; (4) Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 0–1; (5) no history of previous systematic treatment; (6) expected life expectancy of more than 12 weeks; (7) adequate organs function. The key exclusion criteria were history of active autoimmune disease, or concurrent medical use of immunosuppressive medications or immunosuppressive doses of systemic corticosteroids. Eligible patients received camrelizumab 200 mg intravenously every 2 weeks and apatinib 250 mg orally once per day continuously in a treatment cycle of 4 weeks, treatment continued until 1 year or development of unacceptable toxicity or progression of disease. TACE was administrated at the first treatment cycles on day 1or 2, the chemotherapy regimens included 100-150mg oxaliplatin, 750-1000mg fluorouracil, or 30-50 mg lobaplatin, raltitrexed 2-4mg, and epirubicin 40-80 mg. Two or three weeks after the TACE, percutaneous cryoablation was performed under CT guidance. TACE and cryoablation was given as combination therapy and the periods were assessed by the investigator. The primary endpoint is objective response rate (complete or partial response according to mRECIST) and Progression-Free-Survival (Time ranges from random to the first occurrence of disease progression or death from any cause). This trial is registered with Chinese Clinical Trials Registry, ChiCTR2100043044, and is ongoing. Clinical trial information: ChiCTR2100043044.

scholarly journals Avelumab in Combination with Axitinib as First-Line Treatment in Patients with Advanced Hepatocellular Carcinoma: Results from the Phase 1b VEGF Liver 100 Trial

Liver Cancer ◽  
2021 ◽  
pp. 1-11
Author(s):  
Masatoshi Kudo ◽  
Kenta Motomura ◽  
Yoshiyuki Wada ◽  
Yoshitaka Inaba ◽  
Yasunari Sakamoto ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Kinase Inhibitor ◽  
Group Performance ◽  
Objective Response ◽  
Eastern Cooperative Oncology Group ◽  
Clinical Activity ◽  
Advanced Hepatocellular Carcinoma ◽  
Recist 1.1 ◽  
Phase 1B ◽  
Grade 3

<b><i>Introduction:</i></b> Combining an immune checkpoint inhibitor with a targeted antiangiogenic agent may leverage complementary mechanisms of action for the treatment of advanced/metastatic hepatocellular carcinoma (aHCC). Avelumab is a human anti-PD-L1 IgG1 antibody with clinical activity in various tumor types; axitinib is a selective tyrosine kinase inhibitor of vascular endothelial growth factor receptors 1, 2, and 3. We report the final analysis from VEGF Liver 100 (NCT03289533), a phase 1b study evaluating safety and efficacy of avelumab plus axitinib in treatment-naive patients with aHCC. <b><i>Methods:</i></b> Eligible patients had confirmed aHCC, no prior systemic therapy, ≥1 measurable lesion, Eastern Cooperative Oncology Group performance status ≤1, and Child-Pugh class A disease. Patients received avelumab 10 mg/kg intravenously every 2 weeks plus axitinib 5 mg orally twice daily until progression, unacceptable toxicity, or withdrawal. Endpoints included safety and investigator-assessed objective response per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and modified RECIST (mRECIST) for HCC. <b><i>Results:</i></b> Twenty-two Japanese patients were enrolled and treated with avelumab plus axitinib. The minimum follow-up was 18 months as of October 25, 2019 (data cutoff). Grade 3 treatment-related adverse events (TRAEs) occurred in 16 patients (72.7%); the most common (≥3 patients) were hypertension (<i>n</i> = 11 [50.0%]), palmar-plantar erythrodysesthesia syndrome (<i>n</i> = 5 [22.7%]), and decreased appetite (<i>n</i> = 3 [13.6%]). No grade 4 TRAEs or treatment-related deaths occurred. Ten patients (45.5%) had an immune-related AE (irAE) of any grade; 3 patients (13.6%) had an infusion-related reaction (IRR) of any grade, and no grade ≥3 irAE and IRR were observed. The objective response rate was 13.6% (95% CI: 2.9–34.9%) per RECIST 1.1 and 31.8% (95% CI: 13.9–54.9%) per mRECIST for HCC. <b><i>Conclusion:</i></b> Treatment with avelumab plus axitinib was associated with a manageable toxicity profile and showed antitumor activity in patients with aHCC.

A real-world study of camrelizumab in the treatment of hepatocellular carcinoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16121-e16121
Author(s):  
Yong-Yi Zeng ◽  
Wu-hua Guo ◽  
Zhibo Zhang ◽  
Xi Shi ◽  
Yongjie Su ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Clinical Trial ◽  
Real World ◽  
Group Performance ◽  
Objective Response ◽  
Eastern Cooperative Oncology Group ◽  
Chinese Patients ◽  
Advanced Hepatocellular Carcinoma ◽  
Phase Ii Studies ◽  
Clinical Trial Information

e16121 Background: Programmed cell death protein‐1(PD-1) targeted immunotherapy is a promising treatment strategy for advanced hepatocellular carcinoma. Anti-PD-1 inhibitor camrelizumab showed antitumour activity in phase II studies of advanced hepatocellular carcinoma, with manageable toxicities. This study evaluates safety and efficacy of camrelizumab in patients with advanced hepatocellular carcinoma. Methods: This is a multicentre, real‐world trial done at thirty-three centres in Fujian Province, China. Eligible patients were aged 18 to 75 years was diagnosed by China Liver Cancer Staging(CNLC) 2019 clinical diagnostic criteria or with a histological or cytological diagnosis of advanced hepatocellular carcinoma, unresectable or had progressed on or were intolerant to previous systemic treatment, and had an Eastern Cooperative Oncology Group performance score of 0-1. Patients were received camrelizumab 200 mg intravenously every 2 weeks plus other treatments, such as molecular targeted drug, transcatheyer artetial chemoembolization, radiotherapy and chemotherapy. The primary endpoints were progression-free survival. Safety was analysed in all treated patients. Follow-up is ongoing. Results: Between Mar 12, 2020, and Dec 25, 2020, 63 patients were screened for eligibility, of whom 41 eligible patients received camrelizumab were recruited and among whom 15 received apatinib, 16 received lenvatinib, 2 received sorafenib and 1 received regorafenib. Median followup was 5.28 months (IQR 1.63–10.20). Objective response was reported in 12 (29.3%; 95% CI 16.1–45.5) of 41 patients. Disease control was reported in 34 (82.9%; 95% CI 67.9–92.8) of 41 patients. The median PFS was not reached, and expected more than 9 months. Grade 3 or 4 treatment-related adverse events occurred in 21 (51.2%) of 41 patients; the most common were increased gamma-glutamyltransferase (15 [36.6%]) and increased aspartate aminotransferase (7 [17%]). One death was judged by the investigators to be potentially treatment-related (due to upper gastrointestinal bleeding). Conclusions: Camrelizumab showed promising efficacy and safety in pretreated Chinese patients with advanced hepatocellular carcinoma, and might represent a new treatment option for these patients. Clinical trial information: ChiCTR2000041405. Research Sponsor: Jiangsu Hengrui Medicine Co., Ltd. Clinical trial information: ChiCTR2000041405.

Radioembolization in Advanced Hepatocellular Carcinoma

2018 ◽  
Vol 36 (19) ◽  
pp. 1898-1901 ◽  
Author(s):  
Ahsun Riaz ◽  
Robert Lewandowski ◽  
Riad Salem
Keyword(s):  
Hepatocellular Carcinoma ◽  
Portal Vein ◽  
Group Performance ◽  
Performance Status ◽  
Relevant Literature ◽  
Eastern Cooperative Oncology Group ◽  
Distant Metastases ◽  
Advanced Hepatocellular Carcinoma ◽  
Vein Thrombosis ◽  
Management Approaches

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors’ suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice. A 68-year-old man with a remote history of alcohol abuse presented with vague abdominal pain. A review of systems suggested the patient had an Eastern Cooperative Oncology Group performance status 1 (restriction of strenuous physical activity). There were no physical examination findings of note. Laboratory studies disclosed Child-Pugh A liver status (no ascites; no encephalopathy; total bilirubin, 1 mg/dL; albumin, 3.5 g/dL; and international normalized rato, 1.2). The alpha-fetoprotein was mildly elevated (19.5 ng/mL). Magnetic resonance imaging with contrast disclosed an infiltrative mass with extensive malignant right and left portal vein thrombosis ( Fig 1A ) with cavernous transformation of the portal vein. The infiltrative mass ( Fig 2A ) was biopsied, revealing hepatocellular carcinoma. No distant metastases were found on a bone scintigraphy or computerized tomography scan. Given these features, this patient was classified as Barcelona Clinic for Liver Cancer stage C. The patient was referred for management of advanced hepatocellular carcinoma.

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.

Comparative efficacy of second-line treatments for advanced hepatocellular carcinoma: A network meta-analysis.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 545-545 ◽  
Author(s):  
Neehar Parikh ◽  
Alexander Marshall ◽  
Keith D. Huff ◽  
Rachel Savidge ◽  
Keith A. Betts ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Kinase Inhibitors ◽  
Meta Analysis ◽  
Eastern Cooperative Oncology Group ◽  
Indirect Comparison ◽  
Advanced Hepatocellular Carcinoma ◽  
Second Line ◽  
Comparative Efficacy ◽  
Group Status ◽  
Liver Malignancy

545 Background: Hepatocellular carcinoma (HCC) is the most common primary liver malignancy, and is often advanced at the time of diagnosis. This study conducted a network meta-analysis (NMA) to assess the comparative efficacy of second-line (2L) immunotherapy and tyrosine kinase inhibitors (TKIs) without biomarker selection for advanced HCC (aHCC), including nivolumab (NIVO) + ipilimumab (IPI), cabozantinib (CABO), regorafenib (REG), and placebo (PBO). Methods: Randomized trials for CABO and REG (CELESTIAL and RESORCE) were identified through a literature review and included in the NMA. NIVO (1mg/kg) + IPI (3mg/kg) (from CHECKMATE-040) was linked into the evidence network through a matching-adjusted indirect comparison (MAIC) vs. the PBO arm of the CELESTIAL trial. The CELESTIAL trial was chosen due to the similar study design and patient population as the CHECKMATE-040 trial. Clinically relevant characteristics were matched, which included age, sex, Barcelona clinic liver cancer stage, Eastern Cooperative Oncology Group status, α-fetoprotein level, and prior treatments. The NMA included CELESTIAL, RESORCE, and the MAIC results. Investigator-assessed ORR and hazard ratio (HR) of overall survival (OS) were compared in the NMA. Results: After matching the baseline characteristics in the MAIC, the ORR of NIVO+IPI was 30.4% and the HR vs. PBO was 0.35. In the NMA, NIVO+IPI had significantly higher ORR (31.2%) compared to TKIs and PBO (REG: 4.8%; CABO: 4.2%; PBO: 1.0%, differences are presented in Table). In addition, NIVO+IPI was associated with significantly prolonged OS vs. TKIs and PBO (HR: NIVO+IPI vs. REG: 0.56; NIVO+IPI vs. CABO: 0.46; NIVO+IPI vs. PBO: 0.35). Conclusions: The NMA showed that NIVO+IPI was associated with significantly higher ORR and prolonged OS compared to TKIs as 2L treatments for aHCC. [Table: see text]

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