- |||||||||| Review, Journal: The New Era of Systemic Treatment for Hepatocellular Carcinoma: From the First Line to the Optimal Sequence. (Pubmed Central) - Oct 31, 2023
The multi-kinase inhibitor Sorafenib has been the only systemic treatment available for unresectable advanced HCC for almost a decade, but in the last couple of years new therapeutic options have emerged...Currently, first-line systemic treatment for HCC is represented by the combination of the immune checkpoint inhibitor (ICI) Atezolizumab plus Bevacizumab, an anti-vascular endothelial growth factor (VEGF) monoclonal antibody, but many other ICIs have been investigated, such as Nivolumab, Pembrolizumab, Durvalumab and Ipilimumab...The aim of this paper is to offer a complete overview of the most recent innovations in systemic treatments for unresectable locally advanced and metastatic HCC, including emerging therapies, with a particular focus on treatment sequences. Moreover, we will provide an outlook on possible future approaches to patients who progress beyond first-line therapies.
- |||||||||| Journal: Therapeutic inhibition of ATR in differentiated thyroid cancer. (Pubmed Central) - Oct 30, 2023
No appreciable toxicity appeared in animals treated with either a single therapy or a combination treatment. Our findings provide the rationale for the development of clinical trials of BAY 1895344 in the treatment of DTC.
- |||||||||| Avastin (bevacizumab) / Roche, Lenvima (lenvatinib) / Eisai, Merck (MSD), saracatinib (AZD0530) / AstraZeneca
Review, Journal, Tumor mutational burden, IO biomarker: Immunotherapy and Targeted Therapies Efficacy in Thymic Epithelial Tumors: A Systematic Review. (Pubmed Central) - Oct 28, 2023 Combined colchicine and lenvatinib can promote the total anti-cancer effects on HCC. Despite study heterogeneity, this review shows that ICI could be a therapeutic option for selected patients with TET that are not amenable to curative radical treatment after first-line chemotherapy.
- |||||||||| Keytruda (pembrolizumab) / Merck (MSD), Lenvima (lenvatinib) / Eisai, Merck (MSD)
Trial completion: Lenvatinib and Pembrolizumab in Differentiated Thyroid Cancers (DTC) (clinicaltrials.gov) - Oct 24, 2023 P2, N=57, Completed, Together, we unveil CDK6 as a druggable target in lenvatinib-resistant HCC and highlight the use of a chemical biology approach to understand nongenetic resistance mechanisms in cancer. Active, not recruiting --> Completed
- |||||||||| Lenvima (lenvatinib) / Eisai, Merck (MSD)
PK/PD data, Journal: Effects of diet and gender on the pharmacokinetics of oral lenvatinib: A (Pubmed Central) - Oct 22, 2023 High-fat diet altered the pharmacokinetic profile of lenvatinib, but not sufficient to significantly impact its clinical efficacy. Therefore, lenvatinib is suitable for administration under fasted or fed conditions.
- |||||||||| Lenvima (lenvatinib) / Eisai, Merck (MSD), sorafenib / Generic mfg.
Review, Journal: The Evolving Role of Lenvatinib at the New Era of First-Line HCC Treatment. (Pubmed Central) - Oct 22, 2023 Furthermore, in high-burden intermediate-stage HCC, accumulating evidence supports first-line lenvatinib, or in combination with transarterial chemoembolization (TACE), as a preferred treatment option over TACE alone. In this Review, we describe the latest evidence surrounding the evolving role of first-line lenvatinib in HCC.
- |||||||||| Lenvima (lenvatinib) / Eisai, Merck (MSD)
Trial completion, Trial completion date, Combination therapy: A Study to Compare the Efficacy and Safety of Ifosfamide and Etoposide With or Without Lenvatinib in Children, Adolescents and Young Adults With Relapsed and Refractory Osteosarcoma (clinicaltrials.gov) - Oct 17, 2023 P2, N=81, Completed, Active, not recruiting --> Completed Active, not recruiting --> Completed | Trial completion date: Mar 2025 --> Aug 2023
- |||||||||| Review, Journal, Tumor mutational burden, PD(L)-1 Biomarker, IO biomarker: Sequencing Systemic Therapy in Hepatocellular Carcinoma. (Pubmed Central) - Oct 16, 2023
Atezolizumab plus bevacizumab and durvalumab plus tremelimumab remain the treatment of choice among all ICI-containing regimens, unless contraindications to either of the medications exist...Of note, we believe that TKIs (e.g., cabozantinib, regorafenib, lenvatinib, and sorafenib) could be more beneficial in later-line settings to broaden inhibition of other pathways apart from vascular endothelial growth factor (VEGF). When conventional treatment options are exhausted, tissue biopsy may be helpful to reveal rare targetable mutations, such as RET gene fusions.
- |||||||||| Tevimbra (tislelizumab-jsgr) / BeiGene
Enrollment closed, Enrollment change, Combination therapy: BGB-A317-212: To Evaluate the Efficacy and Safety of Tislelizumab in Combination With Lenvatinib in Patients With Selected Solid Tumors (clinicaltrials.gov) - Oct 16, 2023 P2, N=65, Active, not recruiting, When conventional treatment options are exhausted, tissue biopsy may be helpful to reveal rare targetable mutations, such as RET gene fusions. Recruiting --> Active, not recruiting | N=150 --> 65
- |||||||||| Lenvima (lenvatinib) / Eisai, Merck (MSD)
Journal: M2 macrophage inhibits the antitumor effects of Lenvatinib on intrahepatic cholangiocarcinoma. (Pubmed Central) - Oct 13, 2023 Angiogenesis related factors was significantly increased in cholangiocarcinoma cells co-cultured with M2. Compared with M1, M2 macrophages can inhibit the anti-tumor effect of Lenvatinib on cholangiocarcinoma through immune regulation, which may be related to the tumor angiogenesis factor effect of M2 macrophage.
- |||||||||| Trial completion date, Trial primary completion date: International Multicentric Study ARON-1 (clinicaltrials.gov) - Oct 13, 2023
P=N/A, N=1220, Recruiting, Compared with M1, M2 macrophages can inhibit the anti-tumor effect of Lenvatinib on cholangiocarcinoma through immune regulation, which may be related to the tumor angiogenesis factor effect of M2 macrophage. Trial completion date: Nov 2022 --> Dec 2024 | Trial primary completion date: Sep 2022 --> Jun 2024
- |||||||||| Lenvima (lenvatinib) / Eisai, Merck (MSD)
Journal, PD(L)-1 Biomarker, IO biomarker: ZNT1 and Zn2+ control TLR4 and PD-L1 endocytosis in macrophage to improve chemotherapy efficacy against liver tumor. (Pubmed Central) - Oct 10, 2023 Integration of radiologic response into this dataset could help clarify outcomes. Our study proposes a new concept that ZNT1 and zinc regulate endosome endocytosis to maintain surface receptors and zinc supplements might be synergized with chemotherapy to treat inflammation-associated tumors, especially those containing PD-L1+ myeloid cells.
- |||||||||| MK-4830 / Merck (MSD), Keytruda (pembrolizumab) / Merck (MSD)
Enrollment closed, Monotherapy, Metastases: Study of MK-4830 as Monotherapy and in Combination With Pembrolizumab (MK-3475) in Participants With Advanced Solid Tumors (MK-4830-001) (clinicaltrials.gov) - Oct 10, 2023 P1, N=442, Active, not recruiting, Our study proposes a new concept that ZNT1 and zinc regulate endosome endocytosis to maintain surface receptors and zinc supplements might be synergized with chemotherapy to treat inflammation-associated tumors, especially those containing PD-L1+ myeloid cells. Recruiting --> Active, not recruiting
- |||||||||| Lenvima (lenvatinib) / Eisai, Merck (MSD)
Effectiveness of lenvatinib in patients with unresectable hepatocellular carcinoma: A multicenter observational study in Japan (Exhibition area) - Oct 6, 2023 - Abstract #ESMOAsia2023ESMO_Asia_761; As a result of multivariate analysis, low ECOG-PS, low modified ALBI grade, low AFP level, small number of intrahepatic lesions, no bile duct involvement, no portal vein involvement and no extrahepatic involvement at baseline were associated with longer median OS. Conclusions This analysis showed that the effectiveness of lenvatinib in real world practice were consistent with previous reports.
- |||||||||| Avastin (bevacizumab) / Roche, Lenvima (lenvatinib) / Eisai, Merck (MSD), Tecentriq (atezolizumab) / Roche
Impact of metformin, statin, aspirin and insulin on the prognosis of unresectable HCC patients receiving first-line lenvatinib or atezolizumab plus bevacizumab (Exhibition area) - Oct 6, 2023 - Abstract #ESMOAsia2023ESMO_Asia_751; Moreover, patients in metformin group had significantly shorter PFS compared to patients in no-metformin group [respectively, 4.5 months (95% CI 2.9-14.2) vs. 5.8 (95% CI 4.1-34.0); HR 1.6 (95% CI 1.0-2.6) p = 0.0212], as confirmed in multivariate analysis (HR 1.7; 95% CI, 1.1-2.7; p=0.0147).No statistically significant differences in terms of both OS and PFS were found between patients in metformin group and patients in no-metformin group in Lenvatinib arm. Conclusions The present study reports the first analysis focused on the role of metformin in a large double cohort of patients affected by advanced HCC who received Lenvatinib or Atezolizumab plus Bevacizumab, thus showing a negative prognostic role of metformin use in the Atezolizumab plus Bevacizumab group.
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