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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]

Real-world patterns of care and attrition of la/mUC patients eligible for systemic therapy following PD-1/L1 inhibitors are not well understood. In an ambispective chart review of patients with la/mUC after PD-1/L1 discontinuation, only one third received subsequent treatment. Prior to the introduction of novel therapies, real-world outcomes following treatment with PD-1/L1 inhibitor therapy were poor. Introduction: The patterns of care and attrition of locally advanced or metastatic urothelial carcinoma (la/mUC) patients eligible for systemic therapy following PD-1/L1 inhibitors are unclear. The objective of this study was to evaluate the clinical characteristics and treatment patterns among patients with la/mUC following discontinuation of first-line (1L) or second-line (2L) PD-1/L1 inhibitor therapy. Methods: An ambispective, multisite, chart review study was conducted in the United States, including patients with la/mUC. Eligible patients had initiated and subsequently discontinued PD-1/L1 therapy in the 1L or 2L setting for la/mUC between May 2016 and July 2018; with follow-up through October 2019. Patient characteristics, treatments, and overall survival (OS) were described. Patients had the option to complete a 1-time patient reported outcomes (PRO) survey. Results: Among 300 patients included in the chart review, 198 (66%) received 1L PD- 1/L1 inhibitor and 102 (34%) received 2L PD-1/L1 inhibitor. Following discontinuation of PD-1/L1 inhibitor therapy, 34% (n = 68) received subsequent therapy in 2L and 29% (n = 30) in third-line (3L). The median OS post-1L PD-1/L1 inhibitor was 9.4 (95% CI 8.6-NA) and 2.5 months (95% CI 2.24-3.50) for those who received and did not receive subsequent therapy, respectively. Following 2L PD-1/L1 inhibitor discontinuation, the median OS was 5.7 (95% CI 5.1-7.8) and 3.98 (95% CI 3.29-4.87) months for those who received and did not receive subsequent therapy, respectively. Among those with PRO data, 64% reported experiencing cancer-related pain and 29.6% received an opioid. Only 12.7% reported having a caregiver, requiring approximately 13 h/d of service. Conclusion: The symptom and caregiver burden are high among real-world patients with la/mUC who discontinued 1L or 2L PD-1/L1 inhibitors and outcomes are dismal, with a minority receiving subsequent therapy. Patterns of care in the setting of 1L maintenance avelumab and novel agents require further investigation. [ABSTRACT FROM AUTHOR]