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Cabozantinib is a widely used multikinase-inhibitor for the treatment of metastatic renal cell carcinoma (mRCC). This study analyzed the efficacy of cabozantinib in real world, including heavily pretreated patients. Antitumor activity was observed in various treatment lines; moreover, we observed that an alternative treatment schedule improves PFS when compared to continuous dosing. No new safety signals emerged from our analysis. Background: The multikinase-inhibitor Cabozantinib is a widely used treatment strategy in metastatic renal cell carcinoma (mRCC), either in combination with the programmed cell death protein-1 (PD-1) inhibitor nivolumab or as monotherapy. Cabozantinib is given continuously at a dose of 60 mg once daily when used as a single agent and at 40 mg when combined with nivolumab. Treatment-related adverse events (TRAE's) were shown to occur frequently. Objective: We aimed to assess the safety and efficacy of cabozantinib in patients with mRCC. Patients were treated in various lines. Furthermore, we analyzed the impact of an alternative treatment schedule in patients not able to maintain continuous dosing. Patients: This is a single center retrospective study from the Medical University of Vienna. Outcome Measurements and Statistical Analysis: Overall response rates (ORR), progression free survival (PFS) and overall survival (OS) were evaluated for the entire cohort, by treatment line and by treatment schedule. Results: Between January 2014 until April 2021, 71 patients received cabozantinib. Sixty-seven patients were eligible for full evaluation. By IMDC cr iter ia, 32.4%, 59.2%, and 8.5% were classified as favorable, intermediate and poor risk respectively. Cabozantinib was offered as a 2nd-line or 3rd-line treatment in 38.0% and 32.4% of patients, respectively. An alternative treatment schedule was offered in 39.1% of patients. Objective responses were found in 43.3% (CR 6%) of patients and the median PFS was 10.8 months (95% CI: 5.5-16.2). When compared to continuous dosing, an alternative treatment schedule was associated with longer PFS (12.2 months (95% CI: 0-25.5) vs. 6.1 months (95% CI: 0.37-11.8) (P = .014, HR 0.46 (95% CI: 0.24-0.86), respectively) and a lower frequency and severity of TRAE's. Conclusions: Safety and efficacy of cabozantinib in real world is comparable to what has been observed in the pivotal trials, irrespective of the treatment line. An alternative schedule may further improve efficacy and safety. [ABSTRACT FROM AUTHOR]

The role of neutrophils in cancer and metastasis is still debated and controversial since they have been shown to be endowed with both pro- and antitumor functions. These contradictory results seem to be now explained by recent discoveries of tumor-associated neutrophils plasticity and multiple neutrophil subsets. Chemokines and chemokine receptors are known to tightly regulate the release of neutrophils from the bone marrow, their passage into circulation and transmigration into the tissues as well as tumor infiltration. It is emerging that chemokine receptors are differentially expressed by neutrophil subsets and they affect not only their recruitment but also their effector functions. Here we are resuming human and murine data suggesting that therapeutic modulation of neutrophil activity through the targeting of specific chemokines or chemokine receptors can improve their anti-tumoral properties. [ABSTRACT FROM AUTHOR]