- |||||||||| Nexavar (sorafenib) / Bayer, Amgen
Review, Journal: Targeting the eicosanoid pathway in hepatocellular carcinoma. (Pubmed Central) - Jul 13, 2021
In this review, we briefly outline the eicosanoid pathway, describe the mechanisms by which some pathway members either facilitate or counter the development of liver diseases, with the focus on NAFLD/hepatic fibrosis/cirrhosis, and HCC. We describe the link between the eicosanoid pathway, inflammation and these liver diseases, and identify components of the eicosanoid pathway that may be used as potential therapeutic targets in HCC.
- |||||||||| Cabometyx (cabozantinib tablet) / Takeda, Exelixis, Ipsen, Nexavar (sorafenib) / Bayer, Amgen
Journal: Advances in pharmacotherapeutics for hepatocellular carcinoma. (Pubmed Central) - Jul 11, 2021
The emergence of new targeted therapies, such as lenvatinib, have changed the landscape of HCC therapy...The efficacy of second line therapies has only been proven in non-responder or sorafenib-intolerant patients. Unfortunately, studies directly comparing the second-line agents regorafenib, ramucirumab and cabozantinib are still lacking.
- |||||||||| Cabometyx (cabozantinib tablet) / Takeda, Exelixis, Ipsen, Nexavar (sorafenib) / Bayer, Amgen
Clinical, FDA event, Journal: Comparative evaluation of cardiovascular risks among nine FDA-approved VEGFR-TKIs in patients with solid tumors: a Bayesian network analysis of randomized controlled trials. (Pubmed Central) - Jul 11, 2021
In contrast, lenvatinib and vandetanib are ranked to have the most severe cardiotoxicity side impacts. These results may provide information for clinical practice guidelines, implementing strategies in selecting the adequate VEGFR-TKIs, and understanding the cardiovascular toxicity inflicted by the VEGFR-TKIs.
- |||||||||| Retrospective data, Journal: Comparative Efficacy of Atezolizumab plus Bevacizumab and Other Treatment Options for Patients with Unresectable Hepatocellular Carcinoma: A Network Meta-Analysis. (Pubmed Central) - Jul 10, 2021
Indirect comparisons suggested an improved overall survival (OS) with atezolizumab-bevacizumab versus lenvatinib (odds ratio, 0.63 [95% CrI 0.39-1.04]; with 97% Bayesian posterior probability of being superior), nivolumab (0.68 [95% CrI 0.41-1.14]; 94%), sorafenib (0.59 [95% CrI 0.39-0.87]; 99%), SIRT (0.51 [95% CrI 0.32-0.82]; 100%), or placebo/best supportive care (0.40 [95% CrI 0.25-0.64]; 100%). Within the context of indirect comparisons, analyses of OS favored atezolizumab-bevacizumab versus other treatment options for patients with locally advanced or metastatic unresectable HCC.
- |||||||||| lenvatinib / Generic mfg.
Clinical, Journal: Lenvatinib as first-line treatment for advanced thyroid cancer: long progression-free survival. (Pubmed Central) - Jul 10, 2021
In this series of RAI-R DTC patients, with the unique features to have an ECOG 0 or 1 and to be naive for TKI treatments, PFS was the longest among all real-life published so far, with the highest rate of patients with partial response and one of the lowest drug discontinuation rate for AEs. The correct timing of treatment start, the tailoring of the dose, and a proper management of the AEs may have a significant impact on the treatment response to LEN.
- |||||||||| Review, Journal, PD(L)-1 Biomarker, IO biomarker: Molecular therapies for HCC: Looking outside the box. (Pubmed Central) - Jul 9, 2021
Recently, lenvatinib was shown to be non-inferior to sorafenib, while regorafenib, cabozantinib, and ramucirumab were shown to be superior to placebo in patients failing sorafenib...Indeed, encouraging preliminary results of phase I studies of bevacizumab plus atezolizumab and lenvatinib plus pembrolizumab have led to the design of ongoing phase III trials, including both antiangiogenics and immune checkpoint inhibitors in the front-line setting...Importantly, good safety profiles make these drugs suitable for future combinations. In this review, we discuss the most recent data on novel combination strategies and targets, as well as looking ahead to the future role of molecular therapies in the treatment of patients with advanced HCC.
- |||||||||| Lenvima (lenvatinib) / Eisai, Merck (MSD)
Enrollment open, Trial completion date, Trial primary completion date, Monotherapy: Study to Assess the Long-term Safety of Lenvatinib Monotherapy, a Lenvatinib Combination Regimen, or a Comparator Treatment Arm to Cancer Participants in Eisai Sponsored Lenvatinib Trials (clinicaltrials.gov) - Jul 9, 2021
P2, N=50, Recruiting,
In this review, we discuss the most recent data on novel combination strategies and targets, as well as looking ahead to the future role of molecular therapies in the treatment of patients with advanced HCC. Active, not recruiting --> Recruiting | Trial completion date: Jul 2021 --> Mar 2022 | Trial primary completion date: Jul 2021 --> Mar 2022
- |||||||||| Halaven (eribulin mesylate) / Eisai, Lenvima (lenvatinib) / Eisai, Merck (MSD)
Enrollment closed, Metastases: LEADER: Lenvatinib and Eribulin in Advanced Soft Tissue Sarcoma (clinicaltrials.gov) - Jul 8, 2021
P1/2, N=30, Active, not recruiting,
Trial completion date: Jan 2023 --> Nov 2023 Recruiting --> Active, not recruiting
- |||||||||| Nexavar (sorafenib) / Bayer, Amgen
Journal: Targeted Molecular Therapeutic Options for Hepatocellular Carcinoma. (Pubmed Central) - Jul 8, 2021
Kinase inhibitors that modulate growth signals, such as sorafenib and lenvatinib, are commonly employed in targeted molecular therapy for HCC patients. This review covers these agents, highlighting modes of action and providing details on clinical trials.
- |||||||||| mirdametinib (PD-0325901) / SpringWorks Therap, BeiGene
Journal: Discovering the role of VEGF signaling pathway in mesendodermal induction of human embryonic stem cells. (Pubmed Central) - Jul 8, 2021
Treating hESCs with Lenvatinib, a pan-inhibitor of VEGF receptors (VEGFRs), impedes their mesendodermal induction...Similar to the VEGFR inhibitor, MEK inhibitor PD0325901 hinders mesendodermal induction of hESCs...Thus, the MEK-ERK cascade plays an important role for the function of VEGF signaling pathway in the mesendodermal induction of hESCs. All together, this study identifies the critical role of VEGF signaling pathway as well as potential crosstalk of VEGF signaling pathway with other known signaling pathways in mesendodermal differentiation of hESCs.
- |||||||||| Avastin (bevacizumab) / Roche, Nexavar (sorafenib) / Bayer, Amgen
Journal: Hepatocellular carcinoma with portal vein invasion: Non-surgical treatment. (Pubmed Central) - Jul 7, 2021
Lenvatinib, another 1st-line systemic agent, has proven non-inferiority to sorafenib in advanced HCC [3]...Of 336 atezolizumab-bevacizumab treated patients, 38% had macrovascular invasion...A single-center randomized controlled study has demonstrated that transarterial chemoembolization with external beam radiotherapy significantly improved progression-free survival and overall survival compared with sorafenib in patients with macroscopic vascular invasion [5]. Earlier studies reported that transarterial chemoembolization improved overall survival of HCC patients with PVTT compared to supportive care [6,7] Recent meta-analysis indicated that radioembolization was safer and more effective than sorafenib in HCC with PVI [8].
- |||||||||| Avastin (bevacizumab) / Roche, Cabometyx (cabozantinib tablet) / Takeda, Exelixis, Ipsen, Nexavar (sorafenib) / Bayer, Amgen
Journal: New systemic agents for hepatocellular carcinoma: an update 2020. (Pubmed Central) - Jul 7, 2021
Systemic treatment options for advanced HCC have substantially increased over the past years. The combination of atezolizumab and bevacizumab will likely become the new standard of care as it is the first treatment to report improved overall survival compared with sorafenib and the first, and so far only, positive phase 3 clinical trial for an immune-checkpoint inhibitor-containing regimen in advanced HCC.
- |||||||||| Loqtorzi (toripalimab-tpzi) / Shanghai Junshi Biosci, Coherus Biosci, Lenvima (lenvatinib) / Eisai, Merck (MSD)
Trial completion date, Metastases: zs-ICC-2019: Combined Therapy Using Oxaliplatin and Gemcitabine Chemotherapy, Lenvatinib and PD1 Antibody (JS001) for Patients With Advanced and Unresectable Intrahepatic Cholangiocarcinoma (clinicaltrials.gov) - Jul 7, 2021
P2, N=30, Active, not recruiting,
The combination of atezolizumab and bevacizumab will likely become the new standard of care as it is the first treatment to report improved overall survival compared with sorafenib and the first, and so far only, positive phase 3 clinical trial for an immune-checkpoint inhibitor-containing regimen in advanced HCC. Trial completion date: Nov 2020 --> Nov 2021
- |||||||||| Loqtorzi (toripalimab-tpzi) / Shanghai Junshi Biosci, Coherus Biosci, Lenvima (lenvatinib) / Eisai, Merck (MSD)
Enrollment closed, Trial primary completion date, Metastases: zs-ICC-2020: Two-cohort Study of Toripalimab(PD1)+Lenvatnib, or Gemox+Lenvatinib in Advanced Intrahepatic Cholangiocarcinoma (clinicaltrials.gov) - Jul 7, 2021
P2, N=60, Active, not recruiting,
Len +/- Eve demonstrated meaningful clinical activity and tolerability in heavily pre-treated patients with mRCC after disease progression with prior ICI and VEGFR-TKI. Recruiting --> Active, not recruiting | Trial primary completion date: Dec 2020 --> Sep 2021
- |||||||||| Keytruda (pembrolizumab) / Merck (MSD), Jemperli (dostarlimab) / GSK
Review, Journal, MSi-H Biomarker, PD(L)-1 Biomarker, IO biomarker: Endometrial Carcinoma: Immune Microenvironment and Emerging Treatments in Immuno-Oncology. (Pubmed Central) - Jul 4, 2021
The uncontrolled KEYNOTE-158 and GARNET trials have shown high response rates with pembrolizumab and dostarlimab in chemoresistant MSI-high tumors...Similar, encouraging results were obtained for MMR proficient (MMRp) cases treated with a combination of pembrolizumab and the angiogenesis inhibitor lenvatinib...We summarize in this review the current knowledge of the immune environment of EC, both for MMRd and MMRp tumors. We also detail the main clinical data regarding PD-1/PD-L1 inhibitors and discuss the next steps of development for immunotherapy, including various ICI-based combinations planned to limit resistance to immunotherapy.
- |||||||||| Avastin (bevacizumab) / Roche
Review: Angiogenesis Inhibitors for Head and Neck Squamous Cell Carcinoma Treatment: Is There Still Hope? (Pubmed Central) - Jul 2, 2021
All trials were in phase I or II, except one study in phase III on bevacizumab...Endostatin and lenvatinib were well-tolerated and their anticancer effects appeared promising...However, some results appear encouraging, suggesting that further investigations of angiogenesis inhibitors, particularly in combination therapies, for HNSCC patients are warranted. PROSPERO (https://www.crd.york.ac.uk/prospero/), identifier CRD42020157144.
- |||||||||| lenvatinib / Generic mfg.
Clinical, Journal: Lenvatinib-induced acute acalculous cholecystitis in a patient with hepatocellular carcinoma. (Pubmed Central) - Jun 30, 2021
Using the Naranjo adverse drug reaction probability scale, a score of 6 was derived, which indicates that this adverse event was probably caused by lenvatinib. In summary, we present a patient with advanced HCC who underwent repeated episodes of acute acalculous cholecystitis as a rare adverse event associated with lenvatinib.
- |||||||||| lenvatinib / Generic mfg.
Clinical, Journal: Colitis induced by Lenvatinib in a patient with advanced hepatocellular carcinoma. (Pubmed Central) - Jun 30, 2021
After the discontinuation of Lenvatinib, his colitis improved, and he resumed Lenvatinib at a lower dose. Colitis is a rare adverse event of Lenvatinib, and this is the first detailed report of colitis induced by Lenvatinib with endoscopic findings.
- |||||||||| lenvatinib / Generic mfg.
Journal: Pneumothorax during lenvatinib treatment for hepatocellular carcinoma with lung metastasis. (Pubmed Central) - Jun 30, 2021
Herein, we report a case of pneumothorax during lenvatinib treatment for multiple lung metastases of hepatocellular carcinoma in a 71-year-old man. Although the development of pneumothorax during treatment with anticancer agents for lung metastases is well-known, this is the first report of pneumothorax induced by lenvatinib during treatment for lung metastases of hepatocellular carcinoma.
- |||||||||| lenvatinib / Generic mfg.
Clinical, Journal: Huge hepatocellular carcinoma with extrahepatic collateral arteries successfully treated by multidisciplinary treatment including laparoscopic devascularization: a case report. (Pubmed Central) - Jun 30, 2021
A 74-year-old man with multiple huge HCC (4 tumors, 18 cm in diameter) and poor liver function (non-alcoholic steatohepatitis, Child-Pugh score 7) was treated with 6 times of chemoembolization in combination with LDEV, 3 times of ablation therapies, and lenvatinib therapy...Unfortunately, he died 6 months after the final treatment with no recurrence of HCC due to the postoperative complication of primary lung cancer. LDEV is a useful tool to continue effective TACE, and multidisciplinary treatment including chemoembolization and LDEV can cure advanced HCC patients with extrahepatic collaterals and impaired liver function.
- |||||||||| Lenvima (lenvatinib) / Eisai, Merck (MSD)
Enrollment change, Trial completion date, Trial termination, Trial primary completion date, Combination therapy: Lenvatinib and Iodine Therapy in Treating Patients With Radioactive Iodine-Sensitive Differentiated Thyroid Cancer (clinicaltrials.gov) - Jun 29, 2021
P2, N=3, Terminated,
It may be possible to re-initiate lenvatinib treatment with good efficacy against distant metastatic lesions, thereby contributing to long-term survival. N=30 --> 3 | Trial completion date: Feb 2022 --> Jun 2021 | Recruiting --> Terminated | Trial primary completion date: Feb 2022 --> Jun 2021; Study has been abandoned for lack of accrual
- |||||||||| Nexavar (sorafenib) / Bayer, Amgen
[VIRTUAL] EFFICACY ANDA SAFETY IN THYROID CARCINOMA () - Jun 29, 2021 - Abstract #MASCCISOO2021MASCC_ISOO_598;
The recent approval of Lenvatinib opens a new horizon in its treatment...However, the results are inconclusive because of the sample’s shortage. In terms of security, a high number of AE have been observed.Tracking and monitoring AE would be crucial to improve the patients’ quality of life.
- |||||||||| Avastin (bevacizumab) / Roche, Nexavar (sorafenib) / Bayer, Amgen, Tecentriq (atezolizumab) / Roche
Journal: An update on atezolizumab for hepatocellular carcinoma. (Pubmed Central) - Jun 28, 2021
The therapeutic scenario changed dramatically in 2020, when the combination of atezolizumab and bevacizumab proved to be significantly superior to sorafenib and, thus, establishing a new standard of care. In this monograph we provide an update about the safety and efficacy of atezolizumab reported in the clinical trials of HCC, as monotherapy or in combination with other agents.
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