Overall, ASCO
annual meeting concerns or small hepatocellular carcinoma; silent
people, despite the onset of the Chinese people the most, but at ASCO
2013 HCC abstract but rarely seen on the figure of the Chinese people.
This paper screened out of which hepatocellular carcinoma related
research, do a brief introduction. Because of advanced liver cancer
has been the standard treatment with sorafenib way, new developments
are either local or systemic therapy with sorafenib combined with
first-line treatment, or is used as second-line treatment with
sorafenib.
First-line treatment: Use doxorubicin-eluting microspheres TACE (DEB-TACE) + sorafenib two clinical trials
DEB-TACE week before treatment started using sorafenib, in the next six months to accept four times DEB-TACE treatment. There are 50 patients with full participation in the project. Disease control rate of 98%, there is no cure for tumor progression (TTUP), the median time of 11.9 months, which BCLC A / B patients was 22.9 months, C patients was 6.2 months (P = 0.01). The median survival time was 24.5 months (95% CI, 14.3-35), where A / B patients was 33.7 months, C patients was 17.1 months (P = 0.001). Although this is a non-controlled Phase 2 clinical trials, but the results are very exciting. Researchers from John - Johns Hopkins University.
First-line treatment: Sorafenib Sorafenib vs gemcitabine + oxaliplatin (GEMOX)
Randomized, two from the French study. Were included 94 patients with unresectable hepatocellular carcinoma, liver function Child A grade. Of which 29% of portal vein tumor thrombus, extrahepatic metastases 69%. Sorafenib alone and GEMOX combination group: 4 months progression-free survival rates were 54% and 61%, the median progression-free survival time was 4.6 months and 6.2 months, median survival time was 13.0 months ( 10.4-22.2) and 13.5 months (7.5-19.1). The authors GEMOX combined with the safety and efficacy expressed satisfaction and indicated that further exploration. But I Yanzhuo efficacy not see satisfactory place.
First-line treatment: sorafenib + capecitabine + oxaliplatin (SECOX)
Single-arm, multi-center, 2, Hong Kong and Singapore joint research.
51 patients with advanced hepatocellular carcinoma participate in the study, 90% of the patients were BCLC C and 80% had extrahepatic metastases. Tumor response rate was 16% (both partial remission), 62% of patients with tumors stable over eight weeks, with a median time to tumor progression was 5.29 months, median progression-free survival was 5.26 months, median survival was 11.73 months. Satisfied with the results of the overall look forward SECOX program with sorafenib alone in randomized controlled trials.
First / second line therapy: TGF-β inhibitor (LY2157299)
Suitable sorafenib or sorafenib treatment progress of patients included in the study, enrolled patients are elevated AFP, AFP surveillance in order to use the anti-tumor effect. Patients were randomized to receive 160mg / day low dose or 360mg / day of high-dose therapy. 106 patients were included in this study had received sorafenib proportion of patients were 78% and 83%. The median time to tumor progression (TTP) was 12 weeks, in which the low and high dose group were 12.6 weeks and 10.9 weeks; which had not received sorafenib-treated patients, the median TTP was 18.3 weeks. In accordance with the risk factors for liver disease stratification, not drinkers drinkers TTP was significantly longer (12.1 weeks vs 6.1 weeks). 20% of patients the AFP decrease of more than 25%. According to these results, the authors intend to select high-dose LY2157299 for further research.
Second-line treatment: PF-03446962 (ALK-1 monoclonal antibody) in a clinical study
ALK-1 is a specific receptor for TGF-β, PF-03446962 is ALK-1 monoclonal antibody. Sorafenib progression or intolerable 24 patients participated in the study. Safety of the drug can still ,3-4 side effects included thrombocytopenia (12.5%), lipase increased, AST increased, and abdominal pain (the latter three were the incidence of 4.2%). Anti-ALK-1-specific side effects telangiectasia incidence of 8.3%. This group of patients was not observed partial or complete tumor remission after 12 weeks of treatment the tumor control rate was 29.2%, the median TTP was 3.0 months. For seven of these patients, and patients with stable disease drug therapy over 12 weeks relevant (?). Sorafenib as second-line treatment, such data are still acceptable, therefore authors believe that the drug is worth further study.
Markers: VEGF and VEGFR gene polymorphisms with sorafenib treatment related toxicity and efficacy
Authors examined 73 patients with liver cancer tissue samples of VEGF-A, VEGF-C and VEGFR-1, -2, -3 molecules of single nucleotide polymorphism (SNP). C，rs699947 C>A和rs2010963 C>G多态性与各级不良反应及皮肤毒性反应显著相关。">Found that VEGF-A rs833061 T> C, rs699947 C> A and rs2010963 C> G polymorphism and levels of adverse reactions and skin toxicity was significantly correlated. And with all levels of adverse reactions and skin toxicity in patients with progression-free survival and overall survival improved (P value less than .05). Therefore, the detection of these loci may help predict the side effects of anti-angiogenic therapy and efficacy.
Observational studies: HBV-related liver cancer and hepatitis C-related liver expression of VEGF pathway related molecules comparison
First-line treatment: Use doxorubicin-eluting microspheres TACE (DEB-TACE) + sorafenib two clinical trials
DEB-TACE week before treatment started using sorafenib, in the next six months to accept four times DEB-TACE treatment. There are 50 patients with full participation in the project. Disease control rate of 98%, there is no cure for tumor progression (TTUP), the median time of 11.9 months, which BCLC A / B patients was 22.9 months, C patients was 6.2 months (P = 0.01). The median survival time was 24.5 months (95% CI, 14.3-35), where A / B patients was 33.7 months, C patients was 17.1 months (P = 0.001). Although this is a non-controlled Phase 2 clinical trials, but the results are very exciting. Researchers from John - Johns Hopkins University.
First-line treatment: Sorafenib Sorafenib vs gemcitabine + oxaliplatin (GEMOX)
Randomized, two from the French study. Were included 94 patients with unresectable hepatocellular carcinoma, liver function Child A grade. Of which 29% of portal vein tumor thrombus, extrahepatic metastases 69%. Sorafenib alone and GEMOX combination group: 4 months progression-free survival rates were 54% and 61%, the median progression-free survival time was 4.6 months and 6.2 months, median survival time was 13.0 months ( 10.4-22.2) and 13.5 months (7.5-19.1). The authors GEMOX combined with the safety and efficacy expressed satisfaction and indicated that further exploration. But I Yanzhuo efficacy not see satisfactory place.
First-line treatment: sorafenib + capecitabine + oxaliplatin (SECOX)
Single-arm, multi-center, 2, Hong Kong and Singapore joint research.
51 patients with advanced hepatocellular carcinoma participate in the study, 90% of the patients were BCLC C and 80% had extrahepatic metastases. Tumor response rate was 16% (both partial remission), 62% of patients with tumors stable over eight weeks, with a median time to tumor progression was 5.29 months, median progression-free survival was 5.26 months, median survival was 11.73 months. Satisfied with the results of the overall look forward SECOX program with sorafenib alone in randomized controlled trials.
First / second line therapy: TGF-β inhibitor (LY2157299)
Suitable sorafenib or sorafenib treatment progress of patients included in the study, enrolled patients are elevated AFP, AFP surveillance in order to use the anti-tumor effect. Patients were randomized to receive 160mg / day low dose or 360mg / day of high-dose therapy. 106 patients were included in this study had received sorafenib proportion of patients were 78% and 83%. The median time to tumor progression (TTP) was 12 weeks, in which the low and high dose group were 12.6 weeks and 10.9 weeks; which had not received sorafenib-treated patients, the median TTP was 18.3 weeks. In accordance with the risk factors for liver disease stratification, not drinkers drinkers TTP was significantly longer (12.1 weeks vs 6.1 weeks). 20% of patients the AFP decrease of more than 25%. According to these results, the authors intend to select high-dose LY2157299 for further research.
Second-line treatment: PF-03446962 (ALK-1 monoclonal antibody) in a clinical study
ALK-1 is a specific receptor for TGF-β, PF-03446962 is ALK-1 monoclonal antibody. Sorafenib progression or intolerable 24 patients participated in the study. Safety of the drug can still ,3-4 side effects included thrombocytopenia (12.5%), lipase increased, AST increased, and abdominal pain (the latter three were the incidence of 4.2%). Anti-ALK-1-specific side effects telangiectasia incidence of 8.3%. This group of patients was not observed partial or complete tumor remission after 12 weeks of treatment the tumor control rate was 29.2%, the median TTP was 3.0 months. For seven of these patients, and patients with stable disease drug therapy over 12 weeks relevant (?). Sorafenib as second-line treatment, such data are still acceptable, therefore authors believe that the drug is worth further study.
Markers: VEGF and VEGFR gene polymorphisms with sorafenib treatment related toxicity and efficacy
Authors examined 73 patients with liver cancer tissue samples of VEGF-A, VEGF-C and VEGFR-1, -2, -3 molecules of single nucleotide polymorphism (SNP). C，rs699947 C>A和rs2010963 C>G多态性与各级不良反应及皮肤毒性反应显著相关。">Found that VEGF-A rs833061 T> C, rs699947 C> A and rs2010963 C> G polymorphism and levels of adverse reactions and skin toxicity was significantly correlated. And with all levels of adverse reactions and skin toxicity in patients with progression-free survival and overall survival improved (P value less than .05). Therefore, the detection of these loci may help predict the side effects of anti-angiogenic therapy and efficacy.
Observational studies: HBV-related liver cancer and hepatitis C-related liver expression of VEGF pathway related molecules comparison
The study included 131 patients, including hepatitis B-related liver cancer and hepatitis C-related liver cancer
were 72% and 28%. Two groups of patients p-ERK and Raf kinase inhibitor
protein expression undifferentiated. VEGF expression in HCV-related liver cancer rate is higher (95% vs 72%, P = 0.005), H score is also higher (289.5 vs 248.8, P <0.001).
First-line treatment: Pexa-Vec (JX-594) with sequential therapy sorafenib
Pexa-Vex is an oncolytic immunotherapy, in front of the log once introduced. This is from the same researchers reported, not described in detail here. This study concluded that Pexa-Vec intratumoral treatment, then sequential therapy sorafenib toxicities can be tolerated, and in imaging can observe some of the response to treatment.
Epidemiology: Diabetes is an independent risk factor for liver cancer
The past 20 years the UK increased incidence of liver cancer by 40%, while type 2 diabetes is suspected to be a risk factor. This is a case - control study included 724 patients with hepatocellular carcinoma and 340 without HCC patients with chronic liver disease (control group). Liver cancer and control groups diabetes rates were 39% and 10.3%, age, gender, diabetes, hemoglobin disease, cirrhosis, alcoholism and Child classification are risk factors for liver disease, including diabetes odds ratio was 5.74 (3.9- 8.3, P <0.001), multivariate analysis showed that insulin treatment of diabetes is also a risk factor. For liver cancer patients, whether diabetes mellitus and survival time is not relevant; But for patients with hepatocellular carcinoma complicated by diabetes, metformin treatment of longer survival (31 months vs 24 months, P = 0.016, HR = 0.74).
Epidemiology: Sex on the survival of patients with liver cancer relationship
This is coming on the SEER database analysis results, including the 38,250 names HCC patients, of which 76% were male, male and female liver median age at diagnosis was 61 years and 68 years old. Overall survival rate: 55 people under the age of women relative to men's relative risk of 0.83 (95% CI 0.78-0.89); 55 years and above, the relative risk was 0.95 (95% CI 0.92-0.98); 65 years and older, the relative risk was 0.98 (95% CI 0.94-1.01). It appears that gender overall survival for liver cancer protective effect exists only in premenopausal or perimenopausal women. It is good to understand, before age 55 have a sufficient amount of estrogen to protect them.
First-line treatment: Sorafenib postmarketing clinical monitoring
Although sorafenib is FDA approved for patients with advanced liver cancer, regardless of the patient's liver function, but sorafenib two Phase 3 clinical trials are based on the patients of Child A, it will be used for liver function than Child B class of poor patients, clinicians will always have concerns. This is called GIDEON prospective clinical study, a collection of more than 3,000 patients treated with sorafenib data. Overall, side effects and drug-induced side effects in patients with different Child classification similar Which, Child B class patients receiving therapeutic doses larger average, while patients of Child A longer course of treatment. Of Child A and B patients, the median survival time was 4.7 months (95% CI :4.3-5 .2) and 4.4 months (95% CI :3.5-5 .5). For patients with Child B grade, the higher the score, the worse the prognosis: 7 points, 8 points and 9 points in median survival times were: 6.2 months (95% CI :4.9-8 .7), 4.8 months (95% CI :4.1-6 .9) and 3.7 months (95% CI :3.0-5 .1).
=== The following are several clinical trials are recruiting patients, no results can be reported ===
Second-line treatment: Regorafenib
Regorafenib is a VEGFR2-TIE2 tyrosine kinase inhibitor, be regarded as an anti-angiogenic drugs. This is a randomized, double-blind, placebo-controlled Phase 3 clinical trials, target patients during treatment with sorafenib in patients with tumor progression, intends to raise 530 patients. Intends to follow patients were randomized in a 2:1 ratio.
Second-line treatment: Pexa-Vec oncolytic immunotherapy
Research name is called TRAVERSE, designed to assess Pexa-Vec sorafenib as second-line treatment, is a randomized, controlled as best supporting Phase 2b clinical trials. Patients were randomized to receive in accordance with the ratio of 2:1 Pexa-Vec therapy or best supportive care.
First-line treatment: Nintedanib right sorafenib head to head clinical trials
Nintedanib is an oral tyrosine kinase inhibitor targets, including VEGF, PDGF and FGF signaling pathways. In the two clinical studies, patients were randomized to receive in accordance with the ratio of 2:1 nintedanib or sorafenib, is expected by the end of 2013 can be obtained findings.
Second-line treatment: Tivantinib of three clinical trials
Tivantinib the HGF receptor MET inhibitors. This is a three clinical trials, target patient is in the early systemic therapy (including sorafenib) during progression or who can not tolerate, and immunohistochemical staining of tumor tissue confirmed high expression of MET. Plans to raise 303 patients were randomized to receive in accordance with the ratio of 2:1 tivantinib or placebo. Is expected to be completed by mid-2015 study.
First-line treatment: Pexa-Vec (JX-594) with sequential therapy sorafenib
Pexa-Vex is an oncolytic immunotherapy, in front of the log once introduced. This is from the same researchers reported, not described in detail here. This study concluded that Pexa-Vec intratumoral treatment, then sequential therapy sorafenib toxicities can be tolerated, and in imaging can observe some of the response to treatment.
Epidemiology: Diabetes is an independent risk factor for liver cancer
The past 20 years the UK increased incidence of liver cancer by 40%, while type 2 diabetes is suspected to be a risk factor. This is a case - control study included 724 patients with hepatocellular carcinoma and 340 without HCC patients with chronic liver disease (control group). Liver cancer and control groups diabetes rates were 39% and 10.3%, age, gender, diabetes, hemoglobin disease, cirrhosis, alcoholism and Child classification are risk factors for liver disease, including diabetes odds ratio was 5.74 (3.9- 8.3, P <0.001), multivariate analysis showed that insulin treatment of diabetes is also a risk factor. For liver cancer patients, whether diabetes mellitus and survival time is not relevant; But for patients with hepatocellular carcinoma complicated by diabetes, metformin treatment of longer survival (31 months vs 24 months, P = 0.016, HR = 0.74).
Epidemiology: Sex on the survival of patients with liver cancer relationship
This is coming on the SEER database analysis results, including the 38,250 names HCC patients, of which 76% were male, male and female liver median age at diagnosis was 61 years and 68 years old. Overall survival rate: 55 people under the age of women relative to men's relative risk of 0.83 (95% CI 0.78-0.89); 55 years and above, the relative risk was 0.95 (95% CI 0.92-0.98); 65 years and older, the relative risk was 0.98 (95% CI 0.94-1.01). It appears that gender overall survival for liver cancer protective effect exists only in premenopausal or perimenopausal women. It is good to understand, before age 55 have a sufficient amount of estrogen to protect them.
First-line treatment: Sorafenib postmarketing clinical monitoring
Although sorafenib is FDA approved for patients with advanced liver cancer, regardless of the patient's liver function, but sorafenib two Phase 3 clinical trials are based on the patients of Child A, it will be used for liver function than Child B class of poor patients, clinicians will always have concerns. This is called GIDEON prospective clinical study, a collection of more than 3,000 patients treated with sorafenib data. Overall, side effects and drug-induced side effects in patients with different Child classification similar Which, Child B class patients receiving therapeutic doses larger average, while patients of Child A longer course of treatment. Of Child A and B patients, the median survival time was 4.7 months (95% CI :4.3-5 .2) and 4.4 months (95% CI :3.5-5 .5). For patients with Child B grade, the higher the score, the worse the prognosis: 7 points, 8 points and 9 points in median survival times were: 6.2 months (95% CI :4.9-8 .7), 4.8 months (95% CI :4.1-6 .9) and 3.7 months (95% CI :3.0-5 .1).
=== The following are several clinical trials are recruiting patients, no results can be reported ===
Second-line treatment: Regorafenib
Regorafenib is a VEGFR2-TIE2 tyrosine kinase inhibitor, be regarded as an anti-angiogenic drugs. This is a randomized, double-blind, placebo-controlled Phase 3 clinical trials, target patients during treatment with sorafenib in patients with tumor progression, intends to raise 530 patients. Intends to follow patients were randomized in a 2:1 ratio.
Second-line treatment: Pexa-Vec oncolytic immunotherapy
Research name is called TRAVERSE, designed to assess Pexa-Vec sorafenib as second-line treatment, is a randomized, controlled as best supporting Phase 2b clinical trials. Patients were randomized to receive in accordance with the ratio of 2:1 Pexa-Vec therapy or best supportive care.
First-line treatment: Nintedanib right sorafenib head to head clinical trials
Nintedanib is an oral tyrosine kinase inhibitor targets, including VEGF, PDGF and FGF signaling pathways. In the two clinical studies, patients were randomized to receive in accordance with the ratio of 2:1 nintedanib or sorafenib, is expected by the end of 2013 can be obtained findings.
Second-line treatment: Tivantinib of three clinical trials
Tivantinib the HGF receptor MET inhibitors. This is a three clinical trials, target patient is in the early systemic therapy (including sorafenib) during progression or who can not tolerate, and immunohistochemical staining of tumor tissue confirmed high expression of MET. Plans to raise 303 patients were randomized to receive in accordance with the ratio of 2:1 tivantinib or placebo. Is expected to be completed by mid-2015 study.
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