Podcasts about pazopanib

In this JCO PO Article Insights episode, host Harold Tan summarizes Low Kynurenine Levels Among Exceptional Responders on Phase Ib Trial of the HDAC Inhibitor Abexinostat with Pazopanib by Tsang et al, published November 07, 2024. Transcript Harold Nathan Tan: Welcome to JCO Precision Oncology Article Insights, where we explore cutting-edge discoveries in the world of cancer treatment and research. I'm Harold Nathan Tan, your host, and today we're taking a focused look at a compelling phase Ib trial led by Dr. Tsang, which investigates a combination of abexinostat, a histone deacetylase inhibitor, with pazopanib, a VEGF-targeting tyrosine kinase inhibitor, in patients with advanced solid tumors. VEGF inhibition has long been an established therapeutic strategy across a wide range of tumor types, including colorectal, ovarian, sarcoma, and renal cell carcinoma. These agents function by disrupting tumor angiogenesis, effectively limiting oxygen and nutrient delivery to malignant cells and contributing to improved survival outcomes. However, over time, acquired resistance remains a significant challenge. A key mechanism implicated in this resistance involves the upregulation of hypoxia-inducible factor 1-alpha, or HIF-1-alpha for short, a master regulator of angiogenesis that restores VEGF signaling under hypoxic conditions. Interestingly, HIF-1-alpha overexpression is mediated by histone deacetylases, especially HDAC2. Preclinical studies suggest that HDAC2 inhibition can suppress tumor cell migration and downregulate HIF-1-alpha activity, effectively disabling a critical escape pathway used by tumors under VEGF pressure. Moreover, combining HDAC inhibition with VEGF blockade has demonstrated synergy in pazopanib-resistant tumor models, forming a compelling rationale for this dual approach. The phase Ib trial by Tsang et al. was designed to evaluate the safety, tolerability, and preliminary efficacy of this dual-targeted approach in patients with heavily pretreated advanced solid tumors. A dose-expansion cohort focused on individuals with renal cell carcinoma, allowing for more detailed evaluation in this population. A central component of this study was the incorporation of biomarker analysis, particularly regarding HDAC2 expression levels. The results were noteworthy. Patients with high HDAC2 expression achieved a progression-free survival of 7.7 months compared to only 3.5 months in those with low expression. Even more compelling, overall survival reached 32.3 months for those with a high HDAC2 expression versus just 9.2 months for those with low expression. This suggests the potential role for HDAC2 as a predictive biomarker for response to combination HDAC and VEGF-targeted therapy. The authors also explored the metabolic landscape of these patients, conducting metabolomic analysis focused on kynurenine, a key tryptophan catabolite known to contribute to the immune suppression in the tumor microenvironment. Its reduction is driven by HIF-1-alpha and inflammatory cytokines, including interleukin-6 and tumor necrosis factor-alpha. What they found was striking. Exceptional responders, defined as patients with treatment responses lasting more than 3 years, had consistently lower levels of kynurenine both before and after treatment. This finding introduces kynurenine as a potential metabolic biomarker. It suggests that patients with lower kynurenine levels may have a less immunosuppressive microenvironment, making them more responsive to the combined effects of HDAC inhibition and VEGF blockade. Of note, VEGF levels themselves did not significantly differ between responders and nonresponders, highlighting that the treatment benefit is not purely VEGF-mediated but likely driven by epigenetic and metabolic modulation. On the safety front, the combination of abexinostat and pazopanib was generally well tolerated. However, this study did report a correlation between higher plasma concentrations of abexinostat and an increased incidence of thrombocytopenia, a class effect associated with HDAC inhibitors. This trial introduces several key considerations for future research. First, it calls for validation of HDAC2 as a predictive biomarker. If confirmed in larger cohorts, HDAC2 expression could be used to select patients most likely to benefit from HDAC inhibitor-based regimens, transforming how we approach trial enrollment and treatment planning. Second, the link between low kynurenine and exceptional response supports further investigation into how metabolic pathways can influence treatment response to combined HDAC and VEGF inhibition. Overall, HDAC inhibitors hold significant promise in precision oncology. Realizing their full therapeutic potential requires a deeper understanding of HDAC biology, refined combination strategies, and thorough preclinical and clinical evaluations tailored to individual patient profiles. This study exemplifies the potential of epigenetic-metabolic crosstalk as a therapeutic vulnerability and underscores the importance of precision stratification in clinical trial design. As research in this space progresses, the integration of molecular, epigenetic, and metabolic profiling will be essential in optimizing the use of HDAC inhibitors and expanding their role within precision oncology. Thank you for tuning into JCO Precision Oncology Article Insights. Don't forget to subscribe and join us next time as we explore more groundbreaking research shaping the future of oncology. Until then, stay informed and stay inspired.   The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

Discussing four papers that caught our eyes from the last few weeks: Pazopanib vs. placebo following metastatectomy. Always concerning when placebo has an OS advantage. ECOG-ACRIN E2810: https://doi.org/10.1200/JCO.23.01544 Gemcitabine vs. Gem + Paclitaxel (Taxol) in pancreatic cancer patients after FOLFIRINOX: https://doi.org/10.1200/JCO.23.00795 An RNA assay to predict gemcitabine sensitivity: https://doi.org/10.1200/JCO.22.02668 Management of skin cancers with ICIs in kidney transplant patients: https://doi.org/10.1200/JCO.23.02570

Pazopanib, a targeted therapy marketed as Votrient, is used to treat certain cancers. The drug has shown promise as a potential treatment for the rare genetic blood vessel disorder hereditary hemorrhagic telangiectasia (HHT), but when a change in ownership of the drug took place, efforts to develop the drug for HHT ended. That led the patient advocacy organization Cure HHT to step in and sponsor a phase 2/3 trial on its own. We spoke to Marianne Clancy, executive director and senior director of strategic partnerships for Cure HHT about the organization's decision to sponsor a clinical trial, why it felt it was necessary to do, and what other patient organizations can learn from its experience.

Drs Sumanta Pal and Jose A. Karam, MD, discuss neoadjuvant therapy in renal cell carcinoma, including TKIs, immuno-oncology, and the need for more studies to explore the role of neoadjuvant therapy in RCC. Relevant disclosures can be found with the episode show notes on Medscape (https://www.medscape.com/viewarticle/984249). The topics and discussions are planned, produced, and reviewed independently of advertisers. This podcast is intended only for US healthcare professionals. Resources Renal Cell Carcinoma https://emedicine.medscape.com/article/281340-overview Neoadjuvant Treatment in Renal Cell Carcinoma: Transforming Challenges Into Opportunities https://pubmed.ncbi.nlm.nih.gov/35248412/ Axitinib https://reference.medscape.com/drug/inlyta-axitinib-999715#10 Phase 2 Trial of Neoadjuvant Axitinib in Patients With Locally Advanced Nonmetastatic Clear Cell Renal Cell Carcinoma https://pubmed.ncbi.nlm.nih.gov/24560330/ Renal Clear Cell Cancer https://www.ncbi.nlm.nih.gov/books/NBK563230/ Response Evaluation Criteria in Solid Tumors https://radiopaedia.org/articles/response-evaluation-criteria-in-solid-tumours?lang=us Tyrosine Kinase Inhibitors https://www.ncbi.nlm.nih.gov/books/NBK563322/ Tyrosine Kinase Inhibitors and Immunotherapy Combinations in Renal Cell Carcinoma https://pubmed.ncbi.nlm.nih.gov/32215057/ A Phase II Study of Pazopanib in Patients With Localized Renal Cell Carcinoma to Optimize Preservation of Renal Parenchyma https://pubmed.ncbi.nlm.nih.gov/25813447/ Bevacizumab (Rx) https://reference.medscape.com/drug/avastin-mvasi-bevacizumab-342257 Everolimus (Rx) https://reference.medscape.com/drug/afinitor-zortress-everolimus-999101 Nivolumab (Rx) https://reference.medscape.com/drug/opdivo-nivolumab-999989 A Pilot Randomized Study Evaluating Nivolumab (Nivo) Or Nivo + Bevacizumab (Bev) Or Nivo + Ipilimumab (Ipi) in Patients With Metastatic Renal Cell Carcinoma (MRCC) Eligible for Cytoreductive Nephrectomy, Metastasectomy or Post-Treatment Biopsy (Bx) https://ascopubs.org/doi/abs/10.1200/JCO.2019.37.15_suppl.4501 Ipilimumab (Rx) https://reference.medscape.com/drug/yervoy-ipilimumab-999636#10 TNM Classification https://www.ncbi.nlm.nih.gov/books/NBK553187/ A Phase II, Single-Arm Trial of Neoadjuvant Axitinib Plus Avelumab in Patients With Localized Renal Cell Carcinoma Who Are at High Risk of Relapse After Nephrectomy (NEOAVAX) https://pubmed.ncbi.nlm.nih.gov/31023100/ Inferior Venal Caval Thrombus https://emedicine.medscape.com/article/1933035-overview A Phase II Study of Neoadjuvant Axitinib for Reducing the Extent of Venous Tumour Thrombus in Clear Cell Renal Cell Cancer With Venous Invasion (NAXIVA) https://pubmed.ncbi.nlm.nih.gov/35739300/ Surgical Management of Renal Cell Carcinoma With Associated Tumor Thrombus Extending Into the Inferior Vena Cava: A 10-Year Single-Center Experience https://pubmed.ncbi.nlm.nih.gov/30817278/

In this podcast episode, Jean-Yves Blay, MD, PhD, and Robin L. Jones, BSc, MBBS, MRCP, MD(Res), discuss the most important clinical trial data on leveraging TKIs as monotherapy and in combination with chemotherapy or immune checkpoint inhibitors for treatment of soft tissue sarcoma and osteosarcoma.Presenters:Jean-Yves Blay, MD, PhDProfessor of Medical OncologyDepartment of MedicineCentre Leon BerardLyon, FranceRobin L. Jones, BSc, MBBS, MRCP, MD(Res)ProfessorSarcoma UnitRoyal Marsden Hospital and Institute of Cancer ResearchLondon, United KingdomLink to full program, including accompanying downloadable slidesets:https://bit.ly/2ZL9bxq

Prof Srinivas talks to ecancertv at ASCO GU 2015 about the results of a phase II study which looked at the use of pazopanib with weekly paclitaxel in refractory urothelial cancer.

Immunotherapy Forum Video #27: Immunotherapies work well in some, but not in others. Who benefits, and why? Dr. Sumanta (Monty) Pal explains what doctors are learning.

Immunotherapy Forum Video #27: Immunotherapies work well in some, but not in others. Who benefits, and why? Dr. Sumanta (Monty) Pal explains what doctors are learning.

Immunotherapy Forum Video #27: Immunotherapies work well in some, but not in others. Who benefits, and why? Dr. Sumanta (Monty) Pal explains what doctors are learning.

Immunotherapy Forum Video #19: Dr. Lauren Harshman discusses treating kidney cancer with immunotherapy. In this video, she focuses on clinical trials studying PD-1 and PDL-1 agents.

Immunotherapy Forum Video #19: Dr. Lauren Harshman discusses treating kidney cancer with immunotherapy. In this video, she focuses on clinical trials studying PD-1 and PDL-1 agents.

Immunotherapy Forum Video #19: Dr. Lauren Harshman discusses treating kidney cancer with immunotherapy. In this video, she focuses on clinical trials studying PD-1 and PDL-1 agents.

Dr. Guru Sonpavde discusses what he does when he first begins treating a patient recently diagnosed with late stage kidney cancer.

Dr. Guru Sonpavde discusses what he does when he first begins treating a patient recently diagnosed with late stage kidney cancer.

Dr. Guru Sonpavde discusses what he does when he first begins treating a patient recently diagnosed with late stage kidney cancer.

Dr Andreas du Bois talks to ecancer at ASCO 2013 about the phase III clinical trial in women with advanced ovarian cancer that found treatment with the oral targeted drug pazopanib following initial successful chemotherapy extended disease-free survival by an average of 5.6 months, compared to placebo. Pazopanib is an oral drug that blocks several targets involved in the growth of tumors and their blood vessels (angiogenesis). In the study, 940 patients with stage III/IV ovarian, fallopian tube, and primary peritoneal cancer were randomly assigned to receive pazopanib or placebo daily for 24 months. All patients had prior surgery and five or more rounds of chemotherapy that successfully prevented the disease from worsening. Patients were followed for 24 months, on average. The median time to disease worsening (progression-free survival) in the pazopanib and placebo group was 17.9 and 12.3 months, respectively.

Dr Necchi presented the results from a study involving the antiangiogenic drug pazopanib at AACR 2012 in Chicago. The results revealed that increases in interleukin-8 levels early after treatment with pazopanib may predict a lack of tumour response to the therapy.