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Aim: Renal cell carcinoma (RCC) is the seventh commonest cancer in the UK, where first-line (1L) sunitinib and second-line (2L) axitinib are treatment options. Methods: Retrospective, non-interventional data from the Christie NHS Foundation Trust (Manchester, UK). The primary end point was median progression-free survival (mPFS). Results: For 1L sunitinib (n = 622) and 2L axitinib (n = 121), mPFS (95% CI) was 8.4 (7.6, 9.9) and 6.2 (4.9, 9.3) months, respectively. In 1L, Karnofsky performance status, lactate dehydrogenase (LDH), neutrophils, hemoglobin, time from diagnosis to treatment and age were predictors (p < 0.05) of PFS. In 2L, LDH and platelets were predictors of PFS (p < 0.05). Conclusion: Sunitinib and axitinib were effective treatments for RCC. PFS predictors varied between 1L and 2L; LDH was a predictor for both. Clinical Trial Registration:NCT04033991 (ClinicalTrials.gov). Article highlights Renal cell carcinoma (RCC) is the seventh most common type of cancer in the UK. In the UK, axitinib plus avelumab, lenvatinib plus pembrolizumab and nivolumab plus ipilimumab are approved for reimbursement within the NHS. Other approved 1L treatment options include axitinib plus pembrolizumab and cabozantinib plus nivolumab. Previous RCC first-line (1L) mainstay, sunitinib may be a treatment option when ICIs are not appropriate, or single-agent therapy is preferred. Axitinib is recommended as a 2L treatment when not administered in 1L. This study aimed to understand the clinical outcomes of patients with advanced RCC treated with 1L sunitinib and second-line (2L) axitinib in a real-world, UK-based setting, utilizing data extracted from a clinical database held by the Christie NHS Foundation Trust (Manchester, UK). For 1L sunitinib (n = 622), median progression-free survival (PFS) and overall survival (OS) (95% CI) were 8.4 (7.6, 9.9) and 18.3 (15.8, 20.4) months, respectively. For 2L axitinib (n = 121), median PFS and OS (95% CI) were for 6.2 (4.9, 9.3) and 15.8 (12.0, 20.4) months, respectively. Karnofsky performance status, lactate dehydrogenase (LDH), neutrophils, hemoglobin, time from diagnosis to treatment initiation and age were significant (p < 0.05) predictors of PFS for 1L sunitinib. For 2L axitinib, LDH and platelets were significant predictors for PFS. 59 patients received both 1L sunitinib and 2L axitinib. Of the 13 (22.0%) patients who were of favorable IMDC risk at 1L, four (30.8%) remained of favorable risk, eight (61.5%) progressed to intermediate risk and one (7.7%) progressed to poor risk when receiving 2L. Of the 28 (47.5%) patients who were of intermediate risk at 1L, 20 (71.4%) remained of intermediate risk, four (14.3%) progressed to poor risk, but four (14.3%) transitioned to favorable risk during 2L. In a real-world UK setting, 1L sunitinib and 2L axitinib were effective treatments for RCC. Predictors of PFS varied between the 1L and 2L cohorts, with only LDH as a significant predictor for both lines of treatment. 1L sunitinib and 2L axitinib were effective when given in sequence. [ABSTRACT FROM AUTHOR]

Background: The therapeutic benefit of immuno-oncology (IO) therapy for patients with advanced non-clear-cell renal cell carcinoma (nccRCC) remains unclear. Patients and methods: We reviewed clinical data from 93 patients with advanced nccRCC who received first-line systemic therapy including IO combination therapy and tyrosine kinase inhibitor (TKI) monotherapy at our affiliated institutions. Patients were divided based on the period when the treatment was implemented as the standard of care into the IO and TKI eras. Survival and tumor response outcomes were compared between the IO and TKI eras. Results: Of the 93 patients, 50 (54%) and 43 (46%) were categorized as IO era and TKI era groups, respectively. Progression-free survival (PFS) and overall survival (OS) were significantly longer in the IO era than in the TKI era (median PFS: 8.97 vs. 4.96 months, p = 0.0152; median OS: 38.4 vs. 13.5 months, p = 0.0001). After the adjustment using other covariates, the treatment era was an independent factor for PFS (hazard ratio: 0.59, p = 0.0235) and OS (hazard ratio: 0.27, p < 0.0001). Objective response and disease control rates was not significantly different between the treatment eras (26% vs. 16.3%, p = 0.268; 62% vs. 62.8%, p = 0.594). Conclusion: The implementation of IO therapy was significantly associated with longer survival in the nccRCC population. Further studies are needed to establish a more effective treatment strategy in this population using multiple regimens of IO combination therapy. [ABSTRACT FROM AUTHOR]

Purpose: In this study, we evaluated 66 patients diagnosed with adenoid cystic carcinoma (ACC) enrolled in two Korean Cancer Study Group trials to investigate the response and progression patterns in recurrent and/or metastatic ACC treated with vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs). Materials and Methods: We evaluated 66 patients diagnosed with ACC who were enrolled in the Korean Cancer Study Group trials. The tumor measurements, clinical data, treatment outcomes, and progression patterns of therapy were analyzed. Results: In the 66 patients (53 receiving axitinib and 13 receiving nintedanib), the disease control rate was 61%, and three patients achieved partial response. The median follow-up, median progression-free survival (PFS), overall survival, and 6-month PFS rate were 27.6%, 12.4%, and 18.1% months and 62.1%, respectively. Among 42 patients who experienced progression, 27 (64.3%) showed target lesion progression. Bone metastasis was an independent poor prognostic factor. Conclusion: Overall, most patients demonstrated stable disease with prolonged PFS; however, prominent target lesion progression occurred in some patients. Thus, PFS may capture VEGFR-TKI efficacy better than the objective response rate. [ABSTRACT FROM AUTHOR]

Objective: Axitinib is a tyrosine kinase inhibitor characterized by a strong affinity for Vascular Endothelial Growth Factor Receptors (VEGFRs). It was approved in 2012 by Food and Drug Administration and European Medicines Agency as a second line treatment for advanced renal cell carcinoma and is currently under evaluation in clinical trial for the treatment of other cancers. Glioblastoma IDH‐wild type (GBM) is a highly malignant brain tumor characterized by diffusely infiltrative growth pattern and by a prominent neo‐angiogenesis. In GBM, axitinib has demonstrated a limited effectiveness as a monotherapy, while it was recently shown to significantly improve its efficacy in combination treatments. In preclinical models, axitinib has been reported to trigger cellular senescence both in tumor as well as in normal cells, through a mechanism involving intracellular reactive oxygen species (ROS) accumulation and activation of Ataxia Telangiectasia Mutated kinase (ATM). Limiting axitinib‐dependent ROS increase by antioxidants prevents senescence specifically in normal cells, without affecting tumor cells. Methods: We used brain tumor xenografts obtained by engrafting Glioma Stem Cells (GSCs) into the brain of immunocompromised mice, to investigate the hypothesis that the antioxidant molecule N‐Acetyl‐L‐Cysteine (NAC) might be used to reduce senescence‐associated adverse effects of axitinib treatment without altering its anti‐tumor activity. Results: We demonstrate that the use of the antioxidant molecule N‐Acetyl‐Cysteine (NAC) in combination with axitinib stabilizes tumor microvessels in GBM tumor orthotopic xenografts, eventually resulting in vessel normalization, and protects liver vasculature from axitinib‐dependent toxicity. Conclusion: Overall, we found that NAC co‐treatment allows vessel normalization in brain tumor vessels and exerts a protective effect on liver vasculature, therefore minimizing axitinib‐dependent toxicity. [ABSTRACT FROM AUTHOR]

Axitinib (AXTN) is an oral tyrosine kinase inhibitor for the treatment of early to advanced renal cell carcinoma. In this work, solvates of AXTN were prepared in five solvents and subjected to desolvation treatment. The crystal form A of AXTN can form solvates in acetonitrile, DMF, acetic acid, acetic acid + water, and methanol. Different ratios of AXTN and acetic acid will form different products (solvate or directly crystallized into another crystal form (form IV)). The characterization results of thermal analyses confirmed the types of the five solvates. The obtained solvates were desolvated using methods of solid-phase desolvation (heating, exposure to solvent steam, microwave) and solvent-mediated phase transformation (SMPT). The desolvated solids were characterized by PXRD, TGA, DSC, FT-IR, and SEM, and it was ultimately inferred that a new crystal form (form Z) of AXTN could be formed after desolvation. In addition, the solvates obtained in this work experienced mutual transformation via SMPT, which depends on the type of solvents or mixed solvents. The phase transformations of different solid forms were summarized. This study is instructive for exploring solvates and polymorphs of AXTN and understanding phase transitions under different environments. [ABSTRACT FROM AUTHOR]