- |||||||||| Afinitor (everolimus) / Novartis, Sutent (sunitinib) / Pfizer, Cabometyx (cabozantinib tablet) / Takeda, Exelixis, Ipsen
Biomarker, Journal: Identification of mutations associated with acquired resistance to sunitinib in renal cell-cancer. (Pubmed Central) - Jan 19, 2020 Finally, sunitinib resistance induced by continuous exposure or by inhibition of the 6 proteins was overcome by treatment with cabozantinib or a low-dose combination of lenvatinib and everolimus. Collectively, our results unravel novel markers of acquired resistance to sunitinib and clinically relevant approaches for overcoming this resistance in RCC.
- |||||||||| paclitaxel / Generic mfg., Lenvima (lenvatinib) / Eisai, Merck (MSD)
Journal: Lenvatinib vs. palliative therapy for stage IVC anaplastic thyroid cancer. (Pubmed Central) - Jan 14, 2020 However, although a reduction in tumor size by ≥30% was confirmed in 5 patients who received lenvatinib treatment, 2 of those patients succumbed to massive necrosis and bleeding. These results suggest that an appropriate lenvatinib dose reduction is necessary.
- |||||||||| Opdivo (nivolumab) / Ono Pharma, BMS, Cabometyx (cabozantinib tablet) / Takeda, Exelixis, Ipsen
Review, Journal: The Changing Landscape of Systemic Treatment of Advanced Hepatocellular Carcinoma: New Targeted Agents and Immunotherapies. (Pubmed Central) - Jan 11, 2020 In summary, following the approval of sorafenib in 2007 and almost 10 years of therapeutic stagnation, results from recent clinical trials in first- and further-line settings for the first time demonstrated efficacy of several active compounds in advanced HCCs. Thus, a sequential approach should now be implemented in HCC treatment and will improve the survival of HCC patients.
- |||||||||| Cabometyx (cabozantinib tablet) / Takeda, Exelixis, Ipsen, Nexavar (sorafenib) / Bayer, Amgen
Clinical, Journal: Cabozantinib in patients with hepatocellular carcinoma failing previous treatment with sorafenib. (Pubmed Central) - Jan 8, 2020 Recently, lenvatinib was demonstrated noninferior to sorafenib, and regorafenib and ramucirumab were demonstrated superior to placebo in patients progressing on sorafenib and in patients with elevated α-fetoprotein-failing sorafenib, respectively...Furthermore, the study showed a significant improvement in all the efficacy end points. Main adverse events were palmar-plantar erythrodysesthesia, hypertension, increased aspartate aminotransferase, fatigue and diarrhea.
- |||||||||| Stivarga (regorafenib) / Bayer, Lenvima (lenvatinib) / Eisai, Merck (MSD), Nexavar (sorafenib) / Bayer, Amgen
Biomarker, Journal: CRISPR/Cas9 genome-wide screening identifies KEAP1 as a sorafenib, lenvatinib, and regorafenib sensitivity gene in hepatocellular carcinoma. (Pubmed Central) - Jan 8, 2020 Finally, Keap1 disruption also increased the resistance of cells to regorafenib, a recently approved drug to treat HCC as a second line therapy. Taken together, our data indicate that deregulation of the KEAP1/Nrf2 pathway following KEAP1 inactivation contributes to sorafenib, lenvatinib, and regorafenib resistance in human HCC cells through up-regulation of Nrf2 downstream genes and decreased ROS levels.
- |||||||||| Opdivo (nivolumab) / BMS, Lenvima (lenvatinib) / Eisai, Merck (MSD)
Enrollment change, Trial withdrawal: Lenvatinib Plus Nivolumab Versus Lenvatinib for Advanced Hepatocellular Carcinoma With Hepatitis B Virus Infection (clinicaltrials.gov) - Jan 7, 2020 P2b, N=0, Withdrawn, Taken together, our data indicate that deregulation of the KEAP1/Nrf2 pathway following KEAP1 inactivation contributes to sorafenib, lenvatinib, and regorafenib resistance in human HCC cells through up-regulation of Nrf2 downstream genes and decreased ROS levels. N=216 --> 0 | Not yet recruiting --> Withdrawn
- |||||||||| MK-4830 / Merck (MSD), Keytruda (pembrolizumab) / Merck (MSD)
Enrollment change, Trial completion date, Trial primary completion date, 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) - Jan 6, 2020 P1, N=270, Recruiting, If approved by Merck, RSC July 20, 2019 N=70 --> 270 | Trial completion date: Nov 2022 --> Jun 2023 | Trial primary completion date: Nov 2022 --> Jun 2023
- |||||||||| Lenvima (lenvatinib) / Eisai, Merck (MSD)
Review, Journal: Local ablative therapy of oligoprogressive TKI-treated thyroid cancer. (Pubmed Central) - Dec 29, 2019 Both LATs extended the duration of disease control and the time of exposure to the ongoing TKI, thereby indicating that LAT is a favorable option for TKI-treated oligoprogressive thyroid cancer. Prospective randomized studies are needed to verify the benefit of LATs in terms of progression-free and overall survival in this increasingly frequent clinical setting.
- |||||||||| Afinitor (everolimus) / Novartis, Cabometyx (cabozantinib tablet) / Takeda, Exelixis, Ipsen
Clinical, PK/PD data, Journal: Pharmacodynamics, clinical findings and approval status of current and emerging tyrosine-kinase inhibitors for pancreatic neuroendocrine tumors. (Pubmed Central) - Dec 29, 2019 For decades, chemotherapy, somatostatin analogs and interferon represented the only systemic therapies; however, over the latest years, new options were registered, including Everolimus, Sunitinib (SUN), and Peptide Receptor Radionuclide Therapy.Areas covered: This review discusses the role of tyrosine kinase inhibitors (TKIs) in advanced panNETs.Expert opinion: TKIs showed an antiangiogenic and antiproliferative impact on advanced panNETs...New TKIs, such as Cabozantinib, Lenvatinib, Pazopanib, Surufatinib are still on investigation in panNETs...However, it was reported that panNETs resistant to SUN could respond to a new TKIs, indicating a possible further therapeutic line in this context. The global investigation plan of TKIs in panNETs in not homogeneous and it is difficult to understand what kind of development this can have in the near future for clinical practice.
- |||||||||| Opdivo (nivolumab) / Ono Pharma, BMS, Cabometyx (cabozantinib tablet) / Takeda, Exelixis, Ipsen
Developing a Therapeutic Game Plan for the Management of Hepatocellular Carcinoma: Expert Insights From the Patient CaseBook (San Francisco Marriott Marquis, Yerba Buena Ballroom, Salons 10-15) - Dec 28, 2019 - Abstract #ASCOGI2020ASCO-GI_1035; Event Summary The therapeutic management of hepatocellular carcinoma (HCC) has significantly evolved in recent years with the approvals of first-line TKI (lenvatinib) and three targeted therapies (cabozantinib, ramucirumab, and regorafenib) and two checkpoint inhibitors (nivolumab and pembrolizumab) in the second-line setting...Target Audience This activity has been designed to meet the educational needs of medical and gastrointestinal oncologists and other clinicians involved in the management of HCC. Educational Objectives Upon completion of this activity, participants should be better able to: Summarize the safety and efficacy evidence on available multikinase inhibitors for newly diagnosed patients with HCC Review the available treatment options, such as targeted and immune checkpoint therapies, and their associated clinical data for patients with advanced HCC who have progressed after first-line treatment Describe ongoing clinical trials that are studying combination strategies, including immunotherapy with targeted therapy and dual checkpoint inhibitor therapy, for patients with HCC Examine the potential use of systemic treatments, including multikinase and checkpoint inhibitors, in earlier HCC disease settings Develop safe and effective treatment plans across multiple lines of therapy for patients with advanced HCC based on guideline recommendations and validated evidence.
- |||||||||| Loqtorzi (toripalimab-tpzi) / Shanghai Junshi Biosci, Coherus Biosci, Lenvima (lenvatinib) / Eisai, Merck (MSD)
Biomarker, New P2 trial, PD(L)-1 Biomarker, Metastases: Toripalimab Plus Lenvatinib as Second-line Treatment in Advanced Biliary Tract Cancers (clinicaltrials.gov) - Dec 25, 2019 P2, N=44, Not yet recruiting,
- |||||||||| Tevimbra (tislelizumab-jsgr) / BeiGene, Partruvix (pamiparib) / EMD Serono
Enrollment open: BGB-A317-290-LTE1: Study of Tislelizumab, Pamiparib, and Other Investigational Agents in Participants With Advanced Malignancies (clinicaltrials.gov) - Dec 23, 2019 P3, N=300, Enrolling by invitation, Educational Objectives Upon completion of this activity, participants should be better able to: Summarize the safety and efficacy evidence on available multikinase inhibitors for newly diagnosed patients with HCC Review the available treatment options, such as targeted and immune checkpoint therapies, and their associated clinical data for patients with advanced HCC who have progressed after first-line treatment Describe ongoing clinical trials that are studying combination strategies, including immunotherapy with targeted therapy and dual checkpoint inhibitor therapy, for patients with HCC Examine the potential use of systemic treatments, including multikinase and checkpoint inhibitors, in earlier HCC disease settings Develop safe and effective treatment plans across multiple lines of therapy for patients with advanced HCC based on guideline recommendations and validated evidence. Not yet recruiting --> Enrolling by invitation
- |||||||||| Lenvima (lenvatinib) / Eisai, Merck (MSD)
Clinical, Journal: Lenvatinib Real-Life Experience. (Pubmed Central) - Dec 23, 2019 Not yet recruiting --> Enrolling by invitation No abstract available
- |||||||||| Keytruda (pembrolizumab) / Merck (MSD), Lenvima (lenvatinib) / Eisai, Merck (MSD)
Phase III study of first-line pembrolizumab (pembro) plus lenvatinib (len) in patients (pts) with advanced urothelial carcinoma (UC) ineligible for platinum-based chemotherapy: LEAP-011. (Poster Board N15) - Dec 22, 2019 - Abstract #ASCOGU2020ASCO_GU_1334; P1b/2, P2, Clinical trial information: NCT03898180. Research Funding: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA and Eisai Inc., Woodcliff Lake, NJ, USA.
- |||||||||| Keytruda (pembrolizumab) / Merck (MSD), Lenvima (lenvatinib) / Eisai, Merck (MSD)
Phase III study of first-line pembrolizumab (pembro) plus lenvatinib (len) in patients (pts) with advanced urothelial carcinoma (UC) ineligible for platinum-based chemotherapy: LEAP-011. (Poster Board N15) - Dec 22, 2019 - Abstract #ASCOGU2020ASCO_GU_1052; P1b/2, P2, Clinical trial information: NCT03898180. Research Funding: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA and Eisai Inc., Woodcliff Lake, NJ, USA.
- |||||||||| Caprelsa (vandetanib) / Sanofi, Cortone (cortisone acetate) / Merck (MSD), Lenvima (lenvatinib) / Eisai, Merck (MSD)
Journal: PRIMARY ADRENAL INSUFFICIENCY DURING LENVATINIB OR VANDETANIB AND IMPROVEMENT OF FATIGUE AFTER CORTISONE ACETATE THERAPY. (Pubmed Central) - Dec 21, 2019 Patients with PAI received cortisone acetate (CA) replacement therapy, with a significant and prompt improvement in the degree of fatigue, as assessed by the CTCAE Version 4.03, thus supporting the major impact of the impaired adrenal function in the genesis of this adverse event. We show for the first time that the occurrence of PAI may be a frequent cause of fatigue during Lenvatinib and Vandetanib treatment, and we thus recommend testing adrenal function for a prompt start of replacement therapy in order to avoid discontinuation of treatment or dose reduction, as well as potentially severe PAI complications.
- |||||||||| Lenvima (lenvatinib) / Eisai, Merck (MSD)
Journal: Early Relative Change in Hepatic Function with Lenvatinib for Unresectable Hepatocellular Carcinoma. (Pubmed Central) - Dec 19, 2019 Decline in hepatic function is common in the early stage (≤4 weeks, especially within 2 weeks) after introducing LEN. It is important to introduce molecular targeting agent drugs for u-HCC in patients with better hepatic function, who show transarterial catheter chemoembolization failure, as much as possible, along with consideration of the negative influence of LEN on the early response of hepatic function.
- |||||||||| Cabometyx (cabozantinib tablet) / Takeda, Exelixis, Ipsen
Review, Journal: RET fusions in solid tumors. (Pubmed Central) - Dec 19, 2019 Selective RET inhibitor drugs LOXO-292 (selpercatinib) and BLU-667 (pralsetinib) are also undergoing phase I/II and I clinical trials, respectively, with preliminary results demonstrating partial response and low incidence of serious adverse events. RET fusions provide a viable therapeutic target for oncologic treatment, and further study is warranted into the prevalence and pathogenesis of RET fusions as well as development of current and new tyrosine kinase inhibitors.
- |||||||||| Lenvima (lenvatinib) / Eisai, Merck (MSD)
Trial completion date, Trial primary completion date, Combination therapy, Metastases: A Trial to Evaluate Efficacy and Safety of Lenvatinib in Combination With Everolimus in Subjects With Unresectable Advanced or Metastatic Non Clear Cell Renal Cell Carcinoma (nccRCC) Who Have Not Received Any Chemotherapy for Advanced Disease (clinicaltrials.gov) - Dec 19, 2019 P2, N=31, Active, not recruiting, RET fusions provide a viable therapeutic target for oncologic treatment, and further study is warranted into the prevalence and pathogenesis of RET fusions as well as development of current and new tyrosine kinase inhibitors. Trial completion date: Apr 2019 --> Mar 2020 | Trial primary completion date: Apr 2019 --> Mar 2020
- |||||||||| Loqtorzi (toripalimab-tpzi) / Shanghai Junshi Biosci, Coherus Biosci, Lenvima (lenvatinib) / Eisai, Merck (MSD)
Enrollment closed, 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) - Dec 12, 2019 P2, N=30, Active, not recruiting, Recruiting --> Active, not recruiting | Trial completion date: Jan 2020 --> Nov 2020 Recruiting --> Active, not recruiting
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