scholarly journals Liver Transplantation for Hepatocellular Carcinoma after Downstaging or Bridging Therapy with Immune Checkpoint Inhibitors

Cancers ◽  
2021 ◽  
Vol 13 (24) ◽  
pp. 6307
Author(s):  
Qimeng Gao ◽  
Imran J. Anwar ◽  
Nader Abraham ◽  
Andrew S. Barbas
Keyword(s):  
Liver Transplantation ◽  
Liver Transplant ◽  
Checkpoint Inhibitors ◽  
Case Reports ◽  
Milan Criteria ◽  
First Line ◽  
Bridging Therapy ◽  
Post Operative Period ◽  
Control Disease ◽  
First Line Treatment

Liver transplantation offers excellent outcomes for patients with HCC. For those who initially present within the Milan criteria, bridging therapy is essential to control disease while awaiting liver transplant. For those who present beyond the Milan criteria, a liver transplant may still be considered following successful downstaging. Since the introduction of atezolizumab as part of the first-line treatment for HCC in 2020, there has been increasing interest in the use of ICIs as bridging or downstaging therapies prior to liver transplant. A total of six case reports/series have been published on this topic, with mixed outcomes. Overall, liver transplantation can be performed safely following prolonged ICI use, though ICIs may increase the risk of fulminant acute rejection early in the post-operative period. A minimal washout period between the last dose of ICI and liver transplantation has been identified as an important factor predicting transplant outcomes; however, further research is needed.

Applicability of the Milan Criteria for Determining Liver Transplantation as a First-Line Treatment for Hepatocellular Carcinoma

2006 ◽  
Vol 13 (11) ◽  
pp. 1500-1510 ◽  
Author(s):  
Daisuke Morioka ◽  
Kuniya Tanaka ◽  
Ken-ichi Matsuo ◽  
Kazuhisa Takeda ◽  
Michio Ueda ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Transplantation ◽  
Milan Criteria ◽  
Line Treatment ◽  
First Line ◽  
First Line Treatment

scholarly journals Evidence-Based Second-Line Treatment in RAS Wild-Type/Mutated Metastatic Colorectal Cancer in the Precision Medicine Era

2021 ◽  
Vol 22 (14) ◽  
pp. 7717
Author(s):  
Guido Giordano ◽  
Pietro Parcesepe ◽  
Giuseppina Bruno ◽  
Annamaria Piscazzi ◽  
Vincenzo Lizzi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Checkpoint Inhibitors ◽  
Line Treatment ◽  
Second Line ◽  
Wild Type ◽  
First Line ◽  
Braf Mutations ◽  
Mutational Status ◽  
First Line Treatment

Target-oriented agents improve metastatic colorectal cancer (mCRC) survival in combination with chemotherapy. However, the majority of patients experience disease progression after first-line treatment and are eligible for second-line approaches. In such a context, antiangiogenic and anti-Epidermal Growth Factor Receptor (EGFR) agents as well as immune checkpoint inhibitors have been approved as second-line options, and RAS and BRAF mutations and microsatellite status represent the molecular drivers that guide therapeutic choices. Patients harboring K- and N-RAS mutations are not eligible for anti-EGFR treatments, and bevacizumab is the only antiangiogenic agent that improves survival in combination with chemotherapy in first-line, regardless of RAS mutational status. Thus, the choice of an appropriate therapy after the progression to a bevacizumab or an EGFR-based first-line treatment should be evaluated according to the patient and disease characteristics and treatment aims. The continuation of bevacizumab beyond progression or its substitution with another anti-angiogenic agents has been shown to increase survival, whereas anti-EGFR monoclonals represent an option in RAS wild-type patients. In addition, specific molecular subgroups, such as BRAF-mutated and Microsatellite Instability-High (MSI-H) mCRCs represent aggressive malignancies that are poorly responsive to standard therapies and deserve targeted approaches. This review provides a critical overview about the state of the art in mCRC second-line treatment and discusses sequential strategies according to key molecular biomarkers.

Efficacy of immunotherapy in hepatocholangiocarcinoma (HCC-CC): Proof of concept.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16194-e16194
Author(s):  
Osama Diab ◽  
Maloree Khan ◽  
Saqib Abbasi ◽  
Anwaar Saeed ◽  
Anup Kasi ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Line Treatment ◽  
First Line ◽  
Liver Cancers ◽  
First Line Treatment

e16194 Background: Hepatocholangiocarcinoma (HCC-CC) is a rare form of cancer with a poor prognosis. Of all primary liver cancers, the incidence of HCC-CC ranges from 0.4 to 14.2%. HCC-CC is a mixed carcinoma with findings of both hepatocellular carcinoma and cholangiocarcinoma. Immune checkpoint inhibitors are a potent first line treatment in hepatocellular carcinoma with multiple clinical trial showing effectiveness in cholangiocarcinoma. HCC-CC has limited proven treatment options as patients are generally excluded from clinical trials. In this study we reviewed outcomes of patients with HCC-CC who received immune checkpoint inhibitor in a single center. Methods: Records of patients who had a pathological confirmed HCC-CC by a subspecialized hepatic pathologist at the University of Kansas medical center were reviewed. We identified 6 patients with locally advanced unresectable or metastatic HCC-CC that received immune checkpoint inhibitor between February 2017 and January 2021. Baseline characteristics were obtained, as well as best response, line of therapy, and duration of response. Results: Of the six patients 4 (66%) received PD-1 inhibitor alone and 2 (34%) received combination therapy with CTLA-4 inhibitor for the treatment of HCC-CC. There were 3 (50%) females and 6 (100%) with prior hepatitis C infection. four (66%) patients had metastatic disease and 2 had locally unresectable advanced disease. Objective response rate was 83.3%. One patient achieved complete response and had a treatment holiday after receiving treatment for 2 years, and restarted immunotherapy upon relapse. Four patients had a partial response, of which two passed away after disease progression. One patient had stable disease on 2 different lines of immunotherapy then progressed. Of those who responded, one patient received immunotherapy, 3 (50%) received liver directed therapy and two received chemotherapy or Lenvatinib as first line treatment (Table). Conclusions: Immune checkpoint inhibitors demonstrate potential activity in patients with HCC-CC without unexpected side effect in this unmet need high-risk population. Larger studies are needed to confirm activity and efficacy in this setting.[Table: see text]

Safety profile of immune checkpoint inhibitors versus sorafenib as first-line treatment in advanced hepatocellular carcinoma: A meta-analysis of randomized controlled trials.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 315-315
Author(s):  
Alessandro Rizzo ◽  
Giorgio Frega ◽  
Angela Dalia Ricci ◽  
Andrea Palloni ◽  
Simona Tavolari ◽  
...  
Keyword(s):  
Safety Profile ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Meta Analysis ◽  
Controlled Trials ◽  
Line Treatment ◽  
First Line ◽  
Advanced Hcc ◽  
Randomized Controlled ◽  
First Line Treatment

315 Background: Systemic treatment with tyrosine kinase inhibitors such as sorafenib represents the mainstay of advanced-stage hepatocellular carcinoma (HCC). However, survival outcomes remain disappointing, mostly because of the onset of acquired resistance and a suboptimal safety profile, which frequently requires treatment modifications and early discontinuation of treatment – thus, interfering with compliance and long-term outcomes of patients. With immune checkpoint inhibitors (ICIs) quickly expanding as a novel therapeutic option in advanced HCC, the toxicity profiles of these agents should be kept in mind. We performed a meta-analysis with the aim to compare all-grade (G) adverse drug events (ADEs) of ICIs (alone or in combination with other anticancer agents) versus sorafenib monotherapy across randomized controlled trials (RCTs) of first-line treatment for advanced HCC. Methods: Eligible studies included RCTs comparing ICIs versus sorafenib as first-line treatment in HCC. Safety profile from each selected study was investigated for all-G most common ADEs. Outcomes of interest were as follows: pruritus, diarrhea, hand-foot skin reaction (HFSR), fatigue, aspartate aminotransferase (AST) increase, rash, hypertension and decreased appetite. Results were compared by calculating odds ratios (ORs) with 95% confidence intervals (CIs); ORs were combined with Mantel-Haenszel method. All statistical analyses were performed using R studio software. Results: Two RCTs (CheckMate 459, IMbrave 150) involving 1,228 patients were included in the analysis. Patients treated with ICIs showed higher risk of pruritus (OR 1.99, 95% CI = 1.22-3.24) while sorafenib treatment was associated with higher risk of diarrhea (OR 0.26, 95% CI = 0.18-0.37) and HFSR (OR 0.01, 95% CI = 0-0.04). Conversely, no statistically significant differences were observed in terms of fatigue (OR 0.84, 95% CI = 0.45-1.58), AST increase (OR 1.21, 95% CI = 0.78-1.88), rash (OR 0.71, 95% CI = 0.46-1.11), hypertension (OR 0.28, 95% CI = 0.01-9.76) and decreased appetite (OR 0.41, 95% CI = 0.14-1.21) between the two groups. Conclusions: Although the substantial heterogeneities affecting our analyses, ICIs appear feasible in advanced HCC, being endowed with an acceptable safety profile. Beyond activity and efficacy, careful consideration should be given to toxicity while choosing the appropriate first-line treatment in advanced HCC.

scholarly journals Checkpoint inhibitors plus chemotherapy for first-line treatment of advanced non-small cell lung cancer: a systematic review and meta-analysis of randomized controlled trials

2019 ◽  
Vol 5 (9) ◽  
pp. FSO421 ◽  
Author(s):  
Aung Myint Tun ◽  
Kyaw Zin Thein ◽  
Wai Lin Thein ◽  
Elizabeth Guevara
Keyword(s):  
Adverse Events ◽  
Checkpoint Inhibitors ◽  
Meta Analysis ◽  
Objective Response ◽  
Small Cell ◽  
High Grade ◽  
Line Treatment ◽  
Small Cell Lung ◽  
First Line ◽  
First Line Treatment

Background: We conducted a meta-analysis to evaluate the efficacy and safety of upfront add-on immunotherapy for advanced non-small cell lung cancers (NSCLC). Methods: We performed a literature search on first-line chemotherapy ± immunotherapy in NSCLC. We utilized Revman version 5.3 to calculate the estimated pooled hazard ratio for overall survival (OS) and progression-free survival (PFS) and pooled risk ratio for objective response rate (ORR), all-grade and high-grade adverse events with 95% CI. Results: We analyzed 4322 patients. The pooled hazard ratios for OS, PFS and ORR were 0.74 (95% CI: 0.62–0.88; p = 0.0007), 0.62 (95% CI: 0.57–0.68; p = 0.00001) and 1.51 (95% CI: 1.3–1.74; p = 0.00001), respectively. The pooled risk ratios for all-grade and high-grade adverse events were 1.01 (95% CI: 0.99–1.03; p = 0.27) and 1.17 (95% CI: 1.07–1.28; p = 0.0006), respectively. Conclusion: Add-on immunotherapy significantly improves PFS, OS and ORR for the first-line treatment of advanced NSCLC with a reasonable safety profile.

scholarly journals Individualizing Systemic Therapies in First Line Treatment and beyond for Advanced Renal Cell Carcinoma

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3750
Author(s):  
Yasir Khan ◽  
Timothy D. Slattery ◽  
Lisa M. Pickering
Keyword(s):  
Renal Cell ◽  
Checkpoint Inhibitors ◽  
Cell Cancer ◽  
Predictive Biomarkers ◽  
Therapeutic Options ◽  
Current Status ◽  
Vegf Receptor ◽  
Line Treatment ◽  
First Line ◽  
First Line Treatment

Therapeutic options for treating advanced renal cell cancer (RCC) are rapidly evolving. Vascular endothelial growth factor (VEGF)-directed therapy, predominantly VEGF receptor (VEGFr) tyrosine kinase inhibitors (TKIs) had been the most effective first line treatment since 2005 irrespective of International Metastatic RCC Database Consortium (IMDC) risk stratification. However, immune checkpoint inhibitors (ICI) have recently changed the treatment paradigm for advanced RCC particularly as the first-line systemic treatment modality. The combination of Ipilimumab and Nivolumab provides better disease control and long-term outcomes compared with the anti-VEGFr TKI Sunitinib for IMDC intermediate- to poor-risk patients and we now have the option of using ICI with TKI upfront for all IMDC risk groups. This poses a challenge for physicians, both to select the most suitable first line regimen and the most suitable subsequent therapy given the lack of data about sequencing in this setting. This treatment landscape is expected to become more complex with the emerging treatment options. Moreover, these therapeutic options cannot be generalized as significant variability exists between individual’s disease biologies and their physiologies for handling treatment adverse effects. Notable efforts are being made to identify promising predictive biomarkers ranging from neo-antigen load to gene expression profiling. These biomarkers need prospective validation to justify their utility in clinical practice and in treatment decision making. This review article discusses various clinicopathological characteristics that should be carefully evaluated to help select appropriate treatment and discusses the current status of biomarker-based selection.

Efficacy and safety of approved first-line tyrosine kinase inhibitor (TKI) treatment in patients with metastatic renal cell carcinoma (mRCC): A network meta-analysis based on phase II/III randomised clinical trials (RCTs).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e16074-e16074
Author(s):  
Kirsi Manz ◽  
Klaus Fenchel ◽  
Andreas Eilers ◽  
Jon Morgan ◽  
Kirsten Wittling ◽  
...  
Keyword(s):  
Phase Ii ◽  
Checkpoint Inhibitors ◽  
Meta Analysis ◽  
Cochrane Central Register ◽  
Line Treatment ◽  
Efficacy And Safety ◽  
First Line ◽  
Manual Search ◽  
Grade 3 ◽  
First Line Treatment

e16074 Background: During the last decade several novel treatment options including TKIs and immune checkpoint inhibitors have been developed for the treatment of mRCC patients. However, results from direct comparisons (head-to-head RCTs) to determine the optimal treatment are lacking for most of these agents. In this network meta-analysis we attempted to indirectly compare efficacy and safety of first-line TKIs in patients with mRCC. Methods: PubMed, Embase, Medline, the Cochrane Central Register of Controlled Trials were searched (English language only). Abstracts of conferences of relevant medical societies were also included from database inception (January 1, 2007) to January 15, 2019. A systematic manual search (including data requests from the publication authors) was also performed. For the purpose of this network meta-analysis only phase II/III RCTs assessing approved first-line TKI therapy for mRCC were analysed. The analysis was done using the software R with the netmeta package. Progression-free survival (PFS) was the primary endpoint; grade 3 and 4 adverse events (AEs) were secondary endpoints. Results: A database search identified 12 studies meeting the eligibility criteria reporting on 4,460 patients. For PFS cabozantinib and sunitinib were found to be superior to sorafenib, however, when compared to tivozanib, PFS did not significantly differ between the TKIs. Furthermore, tivozanib was found to have the highest probability of being the safest drug as first-line treatment in terms of grade 3 and 4 AEs (ranking safety, p score 0.9344). Conclusions: No significant PFS differences for all TKIs currently used for first-line treatment of mRCC have been found when compared with tivozanib. Compared with all approved TKIs tivozanib appears to be the best choice for first-line treatment of these patients because it has demonstrated the most favourable safety profile. These results may provide guidance to oncologists when making treatment decisions for mRCC patients.

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