- |||||||||| Opdivo (nivolumab) / Ono Pharma, BMS, Cabometyx (cabozantinib tablet) / Takeda, Exelixis, Ipsen
Biomarker, Review, Journal, PD(L)-1 Biomarker, IO Biomarker: Review article: systemic treatment of hepatocellular carcinoma. (Pubmed Central) - Oct 2, 2019 The tyrosine kinase inhibitors sorafenib (first line) and regorafenib (second line) have been approved for hepatocellular carcinoma, and the immune checkpoint inhibitor nivolumab obtained conditional approval for sorafenib-experienced patients in the United States. With lenvatinib in the first line, and cabozantinib and ramucirumab in sorafenib-experienced patients, three more targeted therapies reached their primary endpoint in phase III trials and may soon be added to the treatment armamentarium.
- |||||||||| Keytruda (pembrolizumab) / Merck (MSD)
Biomarker, Trial completion date, Trial primary completion date, Tumor mutational burden, PD(L)-1 Biomarker: KeyImPaCT: A Study of Biomarker-Directed, Pembrolizumab (MK-3475) Based Combination Therapy for Advanced Non-Small Cell Lung Cancer (MK-3475-495/KEYNOTE-495) (clinicaltrials.gov) - Sep 30, 2019 P2, N=318, Recruiting, With lenvatinib in the first line, and cabozantinib and ramucirumab in sorafenib-experienced patients, three more targeted therapies reached their primary endpoint in phase III trials and may soon be added to the treatment armamentarium. Trial completion date: May 2022 --> Jan 2023 | Trial primary completion date: May 2022 --> Jan 2023
- |||||||||| Lenvima (lenvatinib) / Eisai, Merck (MSD)
EXPLORATORY ANALYSIS OF BIOMARKERS ASSOCIATED WITH CLINICAL OUTCOMES OF LENVATINIB IN HEPATOCELLULAR CARCINOMA (Hynes Convention Center, Hall B) - Sep 29, 2019 - Abstract #AASLD2019AASLD_2328; This study demonstrates that RDI is an important predictive factor for longer PFS and confirms the importance of maintaining high RDI during lenvatinib treatment. This exploratory biomarker analysis identified a CAFs-signature associated with adverse events and RDI, which might improve management of lenvatinib treatment in HCC patients.
- |||||||||| Lenvima (lenvatinib) / Eisai, Merck (MSD), Nexavar (sorafenib) / Bayer, Amgen, Visudyne (verteporfin) / Novartis
HEDGEHOG SIGNAL INHIBITORS INCREASE EFFICACY OF ANTI-CANCER DRUGS IN ORGANOID MODELS OF HUMAN HEPATOCELLULAR CARCINOMA (Hynes Convention Center, Hall B) - Sep 29, 2019 - Abstract #AASLD2019AASLD_2142; By inhibiting the hedgehog signaling pathway, GANT61 can significantly enhance the efficacy of sorafenib and lenvatinib to suppress the viability of human primary HCC organoids. Therefore, while using "offensive drugs" in the clinic, we need to use stemness related drugs as "defensive drugs" to maximize the treatment efficacy.
- |||||||||| Lenvima (lenvatinib) / Eisai, Merck (MSD)
IL-17 NEUTRALIZATION AMELIORATES THE EFFICACY OF ANTIANGIOGENIC TREATMENTS OF HEPATOCELLULAR CARCINOMA (Hynes Convention Center, Hall B) - Sep 29, 2019 - Abstract #AASLD2019AASLD_1979; Altogether, these results showed in human HCC a positive correlation between the number of IL-17 infiltrating cells and the increased angiogenic activity. In addition, in vivo results strongly suggest that the use of anti-IL-17 neutralization as adjuvant treatment may significantly improve the efficacy of current antiangiogenic drugs.
- |||||||||| Lenvima (lenvatinib) / Eisai, Merck (MSD)
LENVATINIB ALTERS TUMOR IMMUNE MICROENVIRONMENT FROM ‘COLD’ TO ‘HOT’ IN HEPATOCELLULAR CARCINOMA (Hynes Convention Center, Hall B) - Sep 29, 2019 - Abstract #AASLD2019AASLD_1786; Our novel high-throughput screen system successfully identified FGF19 as a susceptible marker of lenvatinib and MYC as its resistant marker. In the syngeneic xenograft mouse model for HCC, lenvatinib apparently altered tumor immune microenvironment from 'cold' to 'hot'.The findings obtained from this study supportthe therapeutic concept of combining drugs targeting angiogenesis and immunology against immune ‘cold’ HCC.
- |||||||||| Lenvima (lenvatinib) / Eisai, Merck (MSD)
LENVATINIB FOR UNRESECTABLE HEPATOCELLULAR CARCINOMA IN REAL-WORLD PRACTICE – MULTICENTER ANALYSISOF PROGNOSTIC FACTORS (Hynes Convention Center, Hall B) - Sep 29, 2019 - Abstract #AASLD2019AASLD_1784; In patients with large or multinodular intermediate-stage HCC exceeding the up-to-seven criteria with Child-Pugh A liver function, who usually do not benefit from TACE, lenvatinib provides more favorable outcome than TACE. Good hepatic function (mALBI 1/2a) is the best indicator for good prognosis in patients receiving LEN, while potential appetite loss in association with low BMI should be kept in mind in such cases.
- |||||||||| Nexavar (sorafenib) / Bayer, Amgen
UPREGULATION OF SECRETORY CLUSTERIN IN RESPONSE TO SORAFENIB LINKS TO ACQUIRED TREATMENT RESISTANCE OF HEPATOCELLULAR CARCINOMA. (Hynes Convention Center, Hall B) - Sep 29, 2019 - Abstract #AASLD2019AASLD_674; 126 patients (pts) treated with sorafenib (SFN group), 9 pts with regorafenib (RFN group) and 22 pts with lenvatinib (LEN group) from Jun 2008 to Apr 2019, have been enrolled in this study. Clinical and in vitro observations describe a close relationship between sCLU upregulation and SFN resistance in HCC, and suggest that NR-index would be promising for early prediction of SFN effect.
- |||||||||| Keytruda (pembrolizumab) / Merck (MSD), Lenvima (lenvatinib) / Eisai, Merck (MSD)
Journal: Collaborative Review Leads to Concurrent Approval. (Pubmed Central) - Sep 27, 2019 Our results suggest that maintaining an RDI ≥75% during the initial 8 weeks of lenvatinib treatment has a favorable impact on response. In a regulatory first, the FDA has collaboratively reviewed a new cancer treatment with drug agencies in Canada and Australia, allowing for simultaneous approval of lenvatinib in combination with pembrolizumab for the treatment of recurrent endometrial carcinomas.
- |||||||||| Lenvima (lenvatinib) / Eisai, Merck (MSD), Nexavar (sorafenib) / Bayer, Amgen
Biomarker, Clinical, Journal: Clinical guidance for Radioiodine Refractory Differentiated Thyroid Cancer. (Pubmed Central) - Sep 26, 2019 In this review we examine the basic biology of radioiodine refractory disease, and discuss optimal treatment approaches, with specific focus on choice and timing of TKI treatment. This clinical field remains fluid, and directions for future research include exploring biomarkers and considering adjuvant TKI use in certain patient groups.
- |||||||||| Afinitor (everolimus) / Novartis, Opdivo (nivolumab) / Ono Pharma, BMS, Cabometyx (cabozantinib tablet) / Takeda, Exelixis, Ipsen
Clinical, Review, Journal: Second-Line Treatment Landscape for Renal Cell Carcinoma: A Comprehensive Review. (Pubmed Central) - Sep 22, 2019 Nivolumab, cabozantinib, and lenvatinib plus everolimus have recently been approved as second-line treatments. The new agents discussed in this review increase the therapeutic options available and provide physicians with opportunities to individualize treatments for their patients, with a view to improving disease control and survival outcomes.
- |||||||||| Lenvima (lenvatinib) / Eisai, Merck (MSD)
ASSESSMENT OF LIVER FUNCTION USING ALBI SCORE IN PATIENTS TREATED WITH LENVATINIB FOR HEPATOCELLULAR CARCINOMA () - Sep 20, 2019 - Abstract #ILCA2019ILCA_325; The new agents discussed in this review increase the therapeutic options available and provide physicians with opportunities to individualize treatments for their patients, with a view to improving disease control and survival outcomes. In cases where lenvatinib for HCC can be administered for 4 weeks or more, liver function may recover after it worsened once.
- |||||||||| Stivarga (regorafenib) / Bayer, Cabometyx (cabozantinib tablet) / Takeda, Exelixis, Ipsen
MATCHING-ADJUSTED INDIRECT COMPARISON OF CABOZANTINIB VERSUS REGORAFENIB IN ADVANCED HEPATOCELLULAR CARCINOMA () - Sep 20, 2019 - Abstract #ILCA2019ILCA_152; P3 In patients who received second-line treatment after sorafenib and were matched for BL characteristics, cabozantinib was associated with prolonged median PFS and OS compared with regorafenib, whereas regorafenib was associated with lower rates of diarrhea than cabozantinib. However, even after matching, bias may still occur in MAIC due to imbalance in unobserved factors, and it cannot replace a head-to-head randomized control trial.
- |||||||||| Cabometyx (cabozantinib tablet) / Takeda, Exelixis, Ipsen
Biomarker, Review, Journal, IO Biomarker: The role of molecular enrichment on future therapies in hepatocellular carcinoma. (Pubmed Central) - Sep 18, 2019 Positive results in recent phase III clinical trials have confirmed the high value of anti-angiogenic therapies for HCC in both first (sorafenib and lenvatinib) and second line (regorafenib and cabozantinib) treatment modalities...Despite significant progress in our understanding of molecular subclasses of HCC, effective translation of the pre-clinical results into trial design is still missing. We here review important aspects of precision medicine approaches for HCC and delineate key milestones for clinical implementation.
|